Mr. Zuanic: Given your excess of hubris and shortfall in accuracy, I had promised myself that I would not respond to another of your syntactically challenged postings. However, having noted your last two, I would like to commend you on one very accurate statement; that you are indeed 'very short on neurology/CNS disorder.' There are a few corrections that need to be made in consideration of your several errors of fact and interpretation:
1) Your make a reference to 'other drugs for post-stroke rehabilitation.' Could you please tell me what those drugs are? The only drug approved for stroke is t-PA, which has to be given within 3 hours of the stroke, and is dangerous because of the risk of increased cerebral hemorrhage. If you are referring to the use of antidepressants to combat post-stroke dysphoria, anticonvulsants to attenuate impulsivity in frontally damaged patients, neuroleptics or benzodiazepines to calm agitation, or Ritalin to enhance attention and cognitive arousal: any of these off-label uses are compensatory for stroke damage and have limited usefulness. They are not stroke drugs, there are not any as of yet in the US besides t-PA. Janssen's Lubeluzole has an NDA filed, but it has much more problematic data than does citicoline, and has been given within 8 hours of infarct. Its approval is considerably less certain than citicoline's.
2) You make several references to 'manipulation' of the data. You clearly do not have any training in clinical research. The fact that 34% of the placebo group had mild strokes compared to 22% of the drug group illustrates the fact that randomization of patient assignment does not assure even distribution of patient attributes. This is a chronic plague in all human trials. Secondly, your statement that citicoline 'failed' in LOCF analysis (it was significant at .06) misses an important point, what LOCF analysis is. The difference between OC vs LOCF is that in OC, only those patients completing the 3 month followup are analyzed, while in LOCF, all patients are analyzed with their last outcome scores treated as if they occurred at 3 months. In fact, virtually all of the patients who were in the LOCF group, but did not complete the three months, failed to do so because they died. Thus if they died after three days, their data was included as if they had continued for three months. There are some strokes so severe that no treatment prevents death (when critical brainstem regions are affected for instance). In this case the LOCF analysis is less statistically powerful because each group had patients who died, equal outcome regardless of whether they were on drug or placebo. Your insistence that there is some type of plot to manipulate the data does raise valid concern, but not about Interneuron or citicoline.
3)Your comments about mortality rate omit the fact that no stroke drug under development has ever shown a positive effect upon mortality, save one: citicoline in the Japanese Takeda trial. There the mortality effect only emerged after 5-6 months of followup. Mortality was not even an endpoint of the US citicoline trials. The Japanese data is not pivotal, but it is a valuable supplemental source for the NDA, regardless of mode of administration or dosage.
4) Your statement that citicoline is not effective in the first 48 hours 'when most neuronal damage is done' is untrue on the first count, partially untrue on the second. Infarct damage continues to expand through the ischemic penumbra for as much as 5-7 days after the infarct.
There were a number of other errors in your postings, but this is enough. I would suggest that you enhance your knowledge base before making scurrilous and unfounded comments about companies, research, and management. I realize from experience that this will have no effect whatsoever upon your opinionated perspective, but this is a cautionary note to thread members who see it as substantive. NeuroInvestment |
