HALL OF SHAME
By the 1920s, medical researchers had become heroes to many Americans (Lederer, 1995).
By the 21 st Century, performers of Randomized Controlled Trials have become heroes in their own eyes, while the educated population has begun to take a guarded approach to medical fishing expeditions.
The time is near, very near, I predict, that participants in RCTs will be hard to find.
Thoughtless and mindless headache research that I have been following from 1974 will, I repeat, will be (not may or might) the greatest contributor to failure to find human guinea pigs after 2030 or earlier.
Two factors propel patients into RCTs: faith in their doctors and altruism. Once a person is cheated, or feels cheated -- not even a thank-you for participation, no provision for receiving data, or follow-up reports, or post-publication singeing critiques -- well, the writing is on the wall. I am not alone in this perception. Alturism can evaporate far faster than any other positive human attribute.
My article published in 2010 (Expert Rev. Neurother. 10(9), 1409-1422, OPEN ACCESS and attached along with) is a must-read for all RCT participants who look with hope and trust to their medical doctors, and, for all empathic medical doctors of succeeding generations for all time who aspire some day to be participants in RCTs.
As this thread evolves, I will add one head-hanging RCT each time. If the trialist(s) has/have not used the same medication for themselves or for her/his loved one or for one as knowledgeable as a Cardiologist/Neurologist/Physician or the trial falls far short of overarching robust and defensible LOGIC, it enters the
Most of such trials originate in the US of America, with Cardiologists/Neurologists from other countries being sucked into the vortex.
No one controls these trials; the FDA encourages such trials over hapless patients. As America is undoubtedly the most litigious society on Earth, such trialists are playing with fire, just like flunarizine is not use in the US because of its rare potential to cause drug-induced Parkinsonism. Besides legal remedy, the US of A is infamous for a more rapid expression of disgust and settling of scores.
Someone has to stand up for the discipline of Medicine and Neurology.
The single undisputed and non-controversial pharmacological absolute that challenges the putative cortical hyperexcitability-glutamate-migraine nexus is the established therapeutic role of TCAs. Amitriptyline is lipophilic; crosses BBB readily. Prevents migraine effectively (Jackson et al. 2010; Couch 2011). May cause serotonin syndrome (Sternbach 1991; Sporer 1995; Gillman 2010; Boyer and Shannon 2005). Despite promoting sleep and improving depression, can induce convulsive seizure in overdose (Paksu et al. 2014) and lead to mania when used in combination with MAO-inhibitors (de la Fuente et al. 1986) or induced by withdrawal (Dilsaver and Greden 1986) indicating a well-modulated cortical hyperexcitability. Combination of propranolol and amitriptyline, paradoxically, works very well for migraine prophylaxis. Protriptyline, nortriptyline, and venlafaxine are other antidepressants that prevent migraine (Silberstein 2015).
Since ethics is forever an unending debate, I have presented a cast-iron vision of ethical practice in medicine (Gupta, 1999). The antithesis of ethics can be found in "Death of a Salesman" - Arthur Miller, 1949 (1915-2005). When doctors turn salespersons, unethical trails result. As a result, truth dissociated itself from such endeavours. Motive is more important than methods (Denis P. Burkitt).
Attitudes are more important than abilities.
Motives are more important than methods.
Character is more important than cleverness.
Perseverance is more important than power.
And the heart takes precedence over the head (Burkitt, 1992, placed
on page 72, Adaptive Mechanisms of Migraine. Breaking the Migraine
Code. Gupta VK. Nova Science, New York, NY, 2009)
History is unforgiving, and, hindsight enjoys perfect 20/20 vision. Just like pneumoencephalography as a therapy for benign cough-induced headache has become obsolete in the late 20th century (see Gupta VK, Headache. 2005; May;45(5):612-4.; Gupta VK. Med Hypotheses. 2004;62(1):45-8.; Gupta VK.
Int J Clin Pract. 2007 Feb;61(2):345-8), such trials will remain etched in time as medical blunders that simply eased through time.
Till the end of the second decade of the 21st Century, migraine is a classical example of how NOT to carry out research.
This time I attach RCTs on glutamate and migraine:
Cephalalgia. 2014 Feb;34(2):103-13. doi: 10.1177/0333102413499648. Epub 2013 Aug 20.
Randomized, multicenter trial to assess the efficacy, safety and tolerability of a single dose of a novel AMPA receptor antagonist BGG492 for the treatment of acute migraine attacks.
Gomez-Mancilla B1, Brand R, Jürgens TP, Göbel H, Sommer C, Straube A, Evers S, Sommer M, Campos V, Kalkman HO, Hariry S, Pezous N, Johns D, Diener HC; BGG492 Study Group.
Waung MW, Akerman S, Wakefield M, Keywood C, Goadsby PJ. Metabotropic glutamate receptor 5: a target for migraine therapy. Ann Clin Transl Neurol 3, 560-571, 2016.
Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein SD, Johnson KW, Phebus LA, Bleakman D, Ornstein PL, Arnold B, Tepper SJ, Vandenhende F. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia 24, 596-602, 2004.
References:
Lederer SE. Subjected to science: Human experimentation in Americas before the Second World War. Baltimore, John Hopkins University Press, 1995, pp 51-72.
Gupta VK. Does magnesium supplementation have any role in acute myocardial infarction? Cardiovasc. Drugs Ther. 1996, 10, 303-305.
Gupta, J. Medical Ethics 1996, 22, 245, 246, with response from the hen British Medical Journal Editor-in-Chief, Richard Smith and a Journalist/General Practitioner Naomi Craft, 1996, 22, 245-246 with retraction of Editorial policy (removed by BMJ from online access); comments 360-361.
New Delhi 21 Novemeber 2018
ORCiD ID: 0000-0002-6770-5916
My colleagues and I from Johns Hopkins Hospital have reported the 40%-80% of chronic pain patients are misdiagnosed. In one article from the former chairman of neurosurgery at Johns Hopkins Hospital. we looked at 70 patients, referred to us with normal MRI, CT and X-ray who were told that nothing could be done to help their neck pain and headache. We use the Diagnostic Paradigm from www.MarylandClinicalDiagnostics.com and obtained a diagnoses with a 96% correlation with diagnoses of Johns Hopkins Hospital doctors. Base on the accurate diagnosis, we found that 67 of the 70 (96%) of the patients needed the correct medical testing, such as facet blocks, root blocks and provocative discograms. After performing the correct medical testing, we found that 44 of the 67 patients (65%) of patients were candidates from surgery. When this was performed, 41 of the 44 (93%) of the patients who had surgery improved. So from a group of 70 patients told there was nothing to do to help their headaches, 41 (58%) of this group improved with surgery. Clearly, this research confirms that at least 58% of patients with "headaches" are misdiagnosed.
Nelson,
There is a great need for such articles to be put forth, to clear the deadwood that throttles primary headache research, and to forcibly eliminate the very many myths and assumptions that cloud the perspective.
I congratulate you for putting forth this article that will go a long way to shape peer perception, reviewer discretion, and hyperexcitability of the trialists-Manufacturer combine raring to go for randomized clinical trials even without the fall of a hat. I will certainly read your article in-depth and get back to you
Much of migraine research is mired in cortical spreading depression and its offshoots.
I have done my bit. Others must come forward to cut this giant Gordian knot of ignorance that grows in size and impact by the hour. I attach some of my publications.
A concern was expressed some fifty years ago that the volume of scientific literature had at that time been perceived as already having crossed human problem solving capacity.
The literature of migraine is more vast than any other subject on Earth--with both scientific professional and lay fascination contributing endlessly.
I am extremely grateful to ResearchGate for providing a scientific forum outside the clutches of the editor-reviewer-Industry/Manufacturer combine.
My unpublished research far outweighs my published efforts. I am grateful to the very few open-minded reviewers and editors who have let me make it so far.
For anyone who wishes to follow a fascinating journey into the unknown, I suggest a beginning with my invited 1997 article that has a seismic value >1000 on the Richter for migraine research.
I also attach some files that are historical milestones in my Don Quixote-like deconstruction of the migraine research enterprise.
I have torn the heart out of cortical spreading depression. You might have noted disappearance of CSD-related migraine article from ResearchGate.
I have also completed the evolution of benign cough-induced headache.
Best,
Vinod
New Delhi 25 November, 2018
ORCiD ID: 0000-0002-6770-5916
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