Gone (or so it seems) are the days when a study result needed to be replicated before being accepted as “real”.
Long gone are the days where the FDA barely resembled a regulatory agency worthy of the name.
Again, I think Dr. Mandrola is far too kind and circumspect with his language. These are not merely “dualities” of interest. These are outright naked conflicts of interest where the people who generate the data are also considered the experts in the field who are leveraged to “sell” the data…ultimately for the benefit of the device maker and sometimes by happenstance for the benefit of the patient.
I’m not an interventionalist so I have no direct involvement in any of this stuff but while I think FDA regulation of medical therapy has hit rock bottom, it’s laughable regulation of devices has easily smashed through that barrier. This is yet another example of the latter.
I wanted to emphasize one part of a comment I had made below.
Medicine as a profession is an incredible way to be involved in humanity, but there has always been a population of physicians who profess to be in this profession, but by their actions behave more as mercenaries then "missionaries."
I wanted to focus my medical career as a doc that cared for others; I did not see myself going into research, yet circumstances led me to that research path during my years at the U of Chicago. I recalled the petty infighting within the department of pathology--a battle of the egos. I noted with embarassment and shame how some incredibly brilliant mentors harshly interacted with house staff, and even non-medical personnel within the department. I was so traumatized by this that the only way I could sublimate how I felt was to put my feelings into a poem. I have not shared this and other poems during my life with others; this is a first.
Isn’t what happened more an argument to convert Recover IV to a Bayesian analysis with a prior distribution that is informed by the completed study, rather than abandoning Recover IV?
These new ideas speak to the demand for things that make the medical industry big, gigantic, humongous buckaroos and profits. If ever there was a true renaissance in that the medical industry would create fewer patients by providing real health, if would fizzle to a frazzle.
How can us nobodies pressure the system to do the hard work of asking the right questions? Is there an angle, a lever, an approach to correct the course of the ship?
Right? Just watched 2019 documentary film yesterday: Corporate Coup d'etat which kinda gives us the big picture about the situation we're in right now. Stuff no one tells us, yet we witness all around us. Why we feel so helpless about all of this and how 'us nobodies' might shift the gears.
AND... listened to Briahna Joy Gray's interview with a super smart dude who helps coordinate worldwide BDS efforts. Extremely enlightening and encouraging update on how it's all going... thanks to brave and committed 'us nobodies' all over the world. Incredibly inspiring because it's all *working* to help that extremely corrupt 'system' implode!!! Stuff we'd likely we'd never hear about anywhere else. Of course, medicine is part of this huge mess, too.
John, I concur with your conclusions. There is much that is wrong with how trials are run and how results of trials are judged by the so-called FDA. What most lay people and some professionals do not realize is that the FDA equates with a particular panel in a field of medicine or science that are typically members from academic institutions. Frequently, those panels have members with private agendas intertwined with issues of ego and envy.
• I encountered this when presenting data to the FDA's Oncology Drug Advisory Committee (ODAC) for approval of the drug metoclopramide. The studies I had conducted were on patients receiving high-dose cisplatin chemotherapy for lung cancer. We used the anti-emetic metoclopramide given in high doses intravenously. At that time there were no anti-nausea or anti-vomiting drugs to support patients receiving what is called emetogenic chemotherapy. The results were impressive. ODAC rejected approval for metoclopramide. After the hearing, I asked some of the panel members why they had voted no. One replied: we did not get results similar to yours at our institution. Her institution never published results of their experience with metoclopramide in preventing nausea and vomiting for any chemotherapy drug. Another panel member said he rejected approval because there was no placebo arm. Patients getting high-dose cisplatin universally had non-stop vomiting that lasted most of the day. They required hospitalization and often the attending oncologist would use a barbituate to put the patient to sleep, who would still wake up, vomit and then fall back to sleep. Every oncologist knew about the high emetogenicity of i.v. high-dose cisplatin.
• My groups results were published in the leading journals.
Strum SB, McDermed JE, Opfell RW, Riech LP: Intravenous metoclopramide. An effective antiemetic in cancer chemotherapy. JAMA 247:2683-2686, 1982.
Strum SB, McDermed JE, Liponi DF: High-dose intravenous metoclopramide versus combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind crossover comparison of antiemetic efficacy. J Clin Oncol 3:245-51, 1985
• Metoclopramide was immediately approved as an antiemetic when MSK (Memorial Sloan Kettering) published a ten patient trial with ten patients receiving placebo.
• What I had learned while a USPHS fellow at the U of Chicago was that in academia, if you reject a grant then that academic institution will reject your grant. Our studies were conducted in private practice. I had no ammunition to strike back and reject other "colleagues" trial results. If I had been at MSK, I am sure my initial presentation at the FDA would have been approved.
Also, there are many studies in oncology that show a survival benefit with p values of signicance (< p< 0.05) and yet the data on survival benefit may amount to 6 weeks; and this often involves a drug regimen with high frequency of serious side effects. Yet this is approved by the FDA. What we often have is a discrepancy between real world medicine in community practice and that form of medicine practiced in the ivory tower institutions. The devil is in the details. Issues such as quality of life and supportive care needs are often undiscussed.
Lastly, decisions on eligibility often are arbitrary. For example, an age cut-off for heart transplantation makes no sense if someone age 60 has multi-system disease due to a combination of bad genetics and terrible life-style choices versus a patient age 75, rejected from a trial, but with a physiologic age of 60, and in far better health than the above patient. This is what I encountered after my diagnosis of cardiac amyloidosis. I was 74 and the age cut-off was 72. Instead I was given a chemoimmunotherapy treatment that caused CHF with arrhythmias, renal dysfunction, autonomic dysfunction and a horrendous decline in my functionality.
Bottom line: principled medicine has become an oddity. Ethics in our life has taken a backseat to , ego, envy, avarice and ambition (opportunism). We need to replace such unprincipled behavior with humility, benevolence, altruism, and magnanimity.
John Mandrola has introduced us to a topic worthy of a symposium: How do we practice principled medicine? How should we be teaching our children at home and in their schools about how to conduct their life? When do we mandate that what we do as physicians focus on patient outcome an not on physician or healthcare industry income?
There will never be a confirmatory study for DanGer, despite all of its weaknesses. Why would Abiomed support it given the current prevailing view of interventional cardiologists, who are convinced that Impella saves lives. I wouldn't argue that the device does save some lives, but needs to be used in a narrowly defined group where benefit barely outweighs significant risks.
Sadly John, I think this is one of the negatives of industry-sponsored science. There has to be confluence of interests. See also conduction system pacing.
The confluence of interests should certainly point to patient outcomes combined with quality of life. This is the Holy Grail of medicine; it is the TI (Therapeutic Index) the ratio of Benefits to Patient ÷ Adverse Effects.
It is my belief that the failure we are seeing is related to a lack of principles founded in ethics and morality and compromised by greed and ego. This deviance from a principled life has grown worse. It was never great decades ago, but surely it is now at a crisis mode with ramifications in every walk of life. We have met the enemy, and it is us. Pogo.
Thank you, Dr. Strum, for your invaluable input here. Can't tell you how helpful it is to hear from someone like you on this topic. For those of us with no (western) medical training who were raised to simply 'do what the doctor says,' your words and wisdom are like fresh water in the desert. Much appreciation. Deeply sorry for the mal-treatment you've received for your own cardiac condition. Pogo, indeed.
The line between equipoise and lack of equipoise is imprecise. It's a judgement call. It is possible that judgement might be affected by conflicting interests in this case.
Looks like the pump has problems cardiologists should be aware of, nevertheless.
NYT, 3/29/24: "Heart Pump Is Linked to 49 Deaths, the F.D.A. Warns"
https://www.nytimes.com/2024/03/29/health/fda-heart-pump-fatalities.html
But don't ask the company that makes them. They say they're "safe and effective."
https://www.heartrecovery.com/products-and-services/impella
Gone (or so it seems) are the days when a study result needed to be replicated before being accepted as “real”.
Long gone are the days where the FDA barely resembled a regulatory agency worthy of the name.
Again, I think Dr. Mandrola is far too kind and circumspect with his language. These are not merely “dualities” of interest. These are outright naked conflicts of interest where the people who generate the data are also considered the experts in the field who are leveraged to “sell” the data…ultimately for the benefit of the device maker and sometimes by happenstance for the benefit of the patient.
I’m not an interventionalist so I have no direct involvement in any of this stuff but while I think FDA regulation of medical therapy has hit rock bottom, it’s laughable regulation of devices has easily smashed through that barrier. This is yet another example of the latter.
I wanted to emphasize one part of a comment I had made below.
Medicine as a profession is an incredible way to be involved in humanity, but there has always been a population of physicians who profess to be in this profession, but by their actions behave more as mercenaries then "missionaries."
I wanted to focus my medical career as a doc that cared for others; I did not see myself going into research, yet circumstances led me to that research path during my years at the U of Chicago. I recalled the petty infighting within the department of pathology--a battle of the egos. I noted with embarassment and shame how some incredibly brilliant mentors harshly interacted with house staff, and even non-medical personnel within the department. I was so traumatized by this that the only way I could sublimate how I felt was to put my feelings into a poem. I have not shared this and other poems during my life with others; this is a first.
MEN OF MEDICINE
Men of Hippocrates, I too am one,
Now ashamed of what has become
A once noble art turned around
Spiraling quickly from heaven to ground.
Gods we were never, yet closer before,
Now much more base, the art from us torn.
Strive for the heights; compete with each other,
Close eyes and ears to those who smother,
Under ills that mankind gave birth,
that strangle our fellows
And douse out their mirth.
It is time we spoke less of things esoteric,
Filled our hearts with compassion empathetic,
Cried in our souls when we feel others suffer,
Smile and laugh when sick is no more,
Know all men are rich when they seem poor.
Stephen B. Strum, MD
Hyde Park, Chicago 1968
.
The Vaccinated
Are Just
Marching Toward Utopia
.
Isn’t what happened more an argument to convert Recover IV to a Bayesian analysis with a prior distribution that is informed by the completed study, rather than abandoning Recover IV?
These new ideas speak to the demand for things that make the medical industry big, gigantic, humongous buckaroos and profits. If ever there was a true renaissance in that the medical industry would create fewer patients by providing real health, if would fizzle to a frazzle.
How can us nobodies pressure the system to do the hard work of asking the right questions? Is there an angle, a lever, an approach to correct the course of the ship?
Right? Just watched 2019 documentary film yesterday: Corporate Coup d'etat which kinda gives us the big picture about the situation we're in right now. Stuff no one tells us, yet we witness all around us. Why we feel so helpless about all of this and how 'us nobodies' might shift the gears.
AND... listened to Briahna Joy Gray's interview with a super smart dude who helps coordinate worldwide BDS efforts. Extremely enlightening and encouraging update on how it's all going... thanks to brave and committed 'us nobodies' all over the world. Incredibly inspiring because it's all *working* to help that extremely corrupt 'system' implode!!! Stuff we'd likely we'd never hear about anywhere else. Of course, medicine is part of this huge mess, too.
John, I concur with your conclusions. There is much that is wrong with how trials are run and how results of trials are judged by the so-called FDA. What most lay people and some professionals do not realize is that the FDA equates with a particular panel in a field of medicine or science that are typically members from academic institutions. Frequently, those panels have members with private agendas intertwined with issues of ego and envy.
• I encountered this when presenting data to the FDA's Oncology Drug Advisory Committee (ODAC) for approval of the drug metoclopramide. The studies I had conducted were on patients receiving high-dose cisplatin chemotherapy for lung cancer. We used the anti-emetic metoclopramide given in high doses intravenously. At that time there were no anti-nausea or anti-vomiting drugs to support patients receiving what is called emetogenic chemotherapy. The results were impressive. ODAC rejected approval for metoclopramide. After the hearing, I asked some of the panel members why they had voted no. One replied: we did not get results similar to yours at our institution. Her institution never published results of their experience with metoclopramide in preventing nausea and vomiting for any chemotherapy drug. Another panel member said he rejected approval because there was no placebo arm. Patients getting high-dose cisplatin universally had non-stop vomiting that lasted most of the day. They required hospitalization and often the attending oncologist would use a barbituate to put the patient to sleep, who would still wake up, vomit and then fall back to sleep. Every oncologist knew about the high emetogenicity of i.v. high-dose cisplatin.
• My groups results were published in the leading journals.
Strum SB, McDermed JE, Opfell RW, Riech LP: Intravenous metoclopramide. An effective antiemetic in cancer chemotherapy. JAMA 247:2683-2686, 1982.
Strum SB, McDermed JE, Liponi DF: High-dose intravenous metoclopramide versus combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind crossover comparison of antiemetic efficacy. J Clin Oncol 3:245-51, 1985
• Metoclopramide was immediately approved as an antiemetic when MSK (Memorial Sloan Kettering) published a ten patient trial with ten patients receiving placebo.
• What I had learned while a USPHS fellow at the U of Chicago was that in academia, if you reject a grant then that academic institution will reject your grant. Our studies were conducted in private practice. I had no ammunition to strike back and reject other "colleagues" trial results. If I had been at MSK, I am sure my initial presentation at the FDA would have been approved.
Also, there are many studies in oncology that show a survival benefit with p values of signicance (< p< 0.05) and yet the data on survival benefit may amount to 6 weeks; and this often involves a drug regimen with high frequency of serious side effects. Yet this is approved by the FDA. What we often have is a discrepancy between real world medicine in community practice and that form of medicine practiced in the ivory tower institutions. The devil is in the details. Issues such as quality of life and supportive care needs are often undiscussed.
Lastly, decisions on eligibility often are arbitrary. For example, an age cut-off for heart transplantation makes no sense if someone age 60 has multi-system disease due to a combination of bad genetics and terrible life-style choices versus a patient age 75, rejected from a trial, but with a physiologic age of 60, and in far better health than the above patient. This is what I encountered after my diagnosis of cardiac amyloidosis. I was 74 and the age cut-off was 72. Instead I was given a chemoimmunotherapy treatment that caused CHF with arrhythmias, renal dysfunction, autonomic dysfunction and a horrendous decline in my functionality.
Bottom line: principled medicine has become an oddity. Ethics in our life has taken a backseat to , ego, envy, avarice and ambition (opportunism). We need to replace such unprincipled behavior with humility, benevolence, altruism, and magnanimity.
John Mandrola has introduced us to a topic worthy of a symposium: How do we practice principled medicine? How should we be teaching our children at home and in their schools about how to conduct their life? When do we mandate that what we do as physicians focus on patient outcome an not on physician or healthcare industry income?
There will never be a confirmatory study for DanGer, despite all of its weaknesses. Why would Abiomed support it given the current prevailing view of interventional cardiologists, who are convinced that Impella saves lives. I wouldn't argue that the device does save some lives, but needs to be used in a narrowly defined group where benefit barely outweighs significant risks.
Sadly John, I think this is one of the negatives of industry-sponsored science. There has to be confluence of interests. See also conduction system pacing.
The confluence of interests should certainly point to patient outcomes combined with quality of life. This is the Holy Grail of medicine; it is the TI (Therapeutic Index) the ratio of Benefits to Patient ÷ Adverse Effects.
It is my belief that the failure we are seeing is related to a lack of principles founded in ethics and morality and compromised by greed and ego. This deviance from a principled life has grown worse. It was never great decades ago, but surely it is now at a crisis mode with ramifications in every walk of life. We have met the enemy, and it is us. Pogo.
Thank you, Dr. Strum, for your invaluable input here. Can't tell you how helpful it is to hear from someone like you on this topic. For those of us with no (western) medical training who were raised to simply 'do what the doctor says,' your words and wisdom are like fresh water in the desert. Much appreciation. Deeply sorry for the mal-treatment you've received for your own cardiac condition. Pogo, indeed.
The line between equipoise and lack of equipoise is imprecise. It's a judgement call. It is possible that judgement might be affected by conflicting interests in this case.