An overdose of second opinions
Top cancer centers invent recommendations and charge big money
A while back, I saw a 65 year old woman with a new diagnosis of multiple myeloma. She was a wealthy, well connected and health literate. She used those connections to pursue 3 different second opinions. At places like Mayo clinic, MD Anderson and MSKCC. Each of the doctors she saw was a "trialist”— the first or last author on a pharmaceutical company randomized trial.
One doctor recommended Dara-VRD and autotransplant with Rev maintenance. Another Dara-KRD and dara-R maintenance, no auto. Another recommend dara RD, with ventoclax and dara maintenance, and deferred auto, but possible early CAR-T.
The patient printed out information on all these regimens and sought guidance. Each ‘expert’ was adamant. What should she do?
The answer was, of course, every ‘expert’ was making shit up. There was no right answer. Among all these options, we only have a few large randomized studies to provide lamplight in the darkness.
We know that KRD failed to beat VRD, but technically speaking it would be inaccurate to say that trial showed both are ‘equivalent’. We know adding dara to VRD can improve PFS, but no one knows if you live longer vs. if you reserve dara for the next therapy. We know VRD is superior to RD for PFS, and probably OS, but the trial that proved that has such poor post protocol reporting, there are still open questions. Autotransplant improves PFS but not survival or quality of life (Determination), and costs a ton and steals weeks of your life (hospitalization). The only maintenance with a proven survival benefit is R.
The same experts making up recommendations were instrumental in the landscape of myeloma randomized trials which have repeatedly failed to test the most relevant questions (3 vs 3 or 4 vs 3 followed by proper post progression therapy). Instead they favor uninformative, tautological trials that get drugs approved (e.g. 3 vs 2 ad infinitum)
My recommendation was be VRD (+/- dara, pt preference), no auto, and R maintenance. The guiding principle of my strategy was to minimize the number of toxic, costly drugs and procedures unless there is strong evidence the addition helps. Unlike the other doctors, I don’t make money from transplant nor do I consult for any drug companies— I am not conflicted. I also don’t get paid more for seeing more patients (as they do).
But, I also have the good sense to know that any one of us could have the optimal treatment strategy if it were tested in a very large, multi arm randomized trial, and I told the patient as much. The key difference between me and the other doctors was: I am actually caring for the patient, and they just bill the patient for a one time ‘second opinion’
I was reminded of this story when I saw this tweet.
Aaron is right. But I wish to offer a stronger thesis: What mayo clinic, and MD Anderson and other doctors are doing is unethical. They know damned well that their recommendations do not have proven survival benefits in randomized trials. They are making shit up based on unproven surrogate endpoints (MRD) and their own relationships with companies. They and their institutions make money from selling the idea that Mayo is somehow an ‘expert’ in myeloma. What does that mean? There is no good data to prove that given similar patients, they have better outcomes.
To me we live in a bizarre world. Doctors take hundreds of thousands of dollars from pharmaceutical companies and then recommend those costly, toxic drugs to patients for uses that lack good randomized data. The same doctors help the companies design the trials that repeatedly fail to run the right comparisons— which help ensure that their unproven recommendations remain unfalsifiable (you can’t say they are wrong, just that there is no proof they are right). The hospitals make money from autotransplant, and refuse to heed evidence saying it has no survival benefit (DETERMINATION). The doctors make money from second opinions, and don’t care if they confuse the patient while indulging their fantasy of being the best doctor. The system is fundamentally broken. It won’t be reformed from within. Only external pressure can crack it.
The first step you can do: is search your oncologist for drug company payments on open-payments and be skeptical when they take money from Abbvie and recommend venetoclax maintainence.
This is what killed my father in law in 2017. He was extremely healthy -it took a long time to get a diagnosis of amyloidosis (2016) & the local doctor said a bone marrow transplant was essentially the only option for treatment. He picked up the phone & called the Mayo. He was offered a trial -apparently they told him “well if it doesn’t work you can still get the bone marrow transplant.” That is the most unethical advice.
His health deteriorated as he wasted hours driving 2 hours each way to the Mayo for their [stupid] study. No one ever monitored his progression or told him “hey last chance for the bone marrow transplant.” By November of 2016 he had a stroke-induced by an ER visit in which they laid him down & didn’t move him enough to keep circulation going. He worked so hard to recover from the stroke-but was still in the study. (Again where are the ethics people?!) Then by March of 2017 he was in ICU at the Mayo -no one was honest about his condition. He was _dying_. My husband had to make the call to remove the tube. We had two young children at the time & were expecting another.
I will never recommend any one participate in a trial. I will never trust the Mayo again. I should add-despite this my husband & I both got the Covid vaccine & regret it. (Bad side effects for both of us; heart damage for my husband & possibly me too.) we had moderna & there is more bad news each month on what was essentially a drug trial on all of us.
This was a great post. In view of the financial relationships of the consultants, should they not disclose their financial involvements with the companies and institutions they recommend all detailed with their consultations.