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Stephen Strum, MD, FACP's avatar

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?

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Crixcyon's avatar

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.

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