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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by ed_uk on February 18, 2005, at 10:01:19
From the Pharmaceutical Journal.........
Concerns about the reporting of clinical trial results in medical journals have recently been expressed in a variety of forums.
For example, one of the topics of a speech given by Richard Smith, former editor of the BMJ, was the ways in which the results of clinical trials can be presented to appear favourably to companies with new drugs for which they are seeking marketing approval.1
Dr Smith’s presentation was made as he received the 2004 award, from HealthWatch, a registered charity that aims to support and encourage the scientific testing of conventional, complementary and alternative medicine and therapies. Examples highlighted by Dr Smith include:
· Comparing a new drug with a placebo or too low a dose of a competitor’s drug
· Comparing a new drug with too high a dose of a competitor’s drug, so that it looks as though the new drug has fewer side effects
· Carrying out just a small-scale trial comparing a new drug to a better, but more expensive treatment, so that the results show that there is “no significant difference” between the two agents, thereby making the new drug appear to be good value for money
· Reporting just the end-points of a clinical trial in which a new drug performed well
· Reporting just the results of particular groups of patients, or patients from particular centres in a multi-centre trial, in which a new drug performed well
· Not publishing clinical trial results at all, if there is no subgroup that does well
· Publishing good studies more than once by including, for example, different outcome measurements or the results from different follow-up periods in separate papers
· Publishing positive results in major journals and negative or neutral results in minor journals
As an illustration of these methods being used, Dr Smith cited one particular drug about which there were publications describing 84 trials on 11,980 patients. In fact, there were only 70 trials involving 8,645 patients, but 17 per cent of the trials had been published more than once. This was not identifiable from the published studies. He went on to demonstrate how the multiple publication of trials could increase apparent effectiveness, using an example of how 16 trials showing a number needed to treat (NNT) of nine could be presented as 25 trials showing a NNT of five, by duplicating the results of the most favourable trials.
In a similar vein, members of Parliament heard just before Christmas from Richard Horton, editor of The Lancet, about ways in which pharmaceutical companies attempt to influence the editing of clinical trials reports they have submitted for publication. Dr Horton told the House of Commons Select Committee inquiry, set up to investigate the influence of the pharmaceutical industry, about how drug companies sometimes imply that there is a link between their submission of a paper with revenue for medical journals, from reprints.After submission, authors or sponsors might then try to intervene to move the peer review process along in directions that are less critical of their drug.2
Dr Horton gave as an example an unnamed company that had threatened to withdraw a paper on a cyclo-oxygenase-2 inhibitor because it believed that the review process was over-critical. The company stopped interfering after the paper’s authors had been told that the paper would be rejected unless the company backed off, he said.
There has also been criticism of the way in which clinical trials are reported and analysed once a drug has received marketing approval. A recent paper in The Lancet concluded that the concerns about the cardiac safety of rofecoxib should have been known by the end of 2000, and hence the drug withdrawn earlier than it was.3 Their study was based on the results of 18 randomised controlled trials and 11 observational studies incorporating 20,000 patients. It should, however, be pointed out that the manufacturers of rofecoxib did not agree with this assertion, stating that the authors had inappropriately combined heterogenous data, which runs counter to the basic principles of meta-analysis.4
Among the conclusions that seem appropriate to draw from all this information is that it is important that those carrying out meta-analyses of clinical trial reports, or reviewing such literature with a view to prescribing a drug or informing clinical practice, read the equivalent of the “small print” in the original papers. Whatever the vigilance exercised by pharmacists and others carrying out such activities, a fair reflection of a drug’s safety and efficacy will be hard to achieve if trial results have been published more than once (this not being evident from the reports) or if unfavourable results have not been published at all. Dr Smith’s suggestions of a register of all trials, so that unfavourable trials do not “disappear”, critical review of trial protocols by independent experts, publication of trials in online journals that do not rely on commercial sponsorship for revenue and more public funding for clinical trials, seem to be particularly worthwhile aims.
Posted by med_empowered on February 18, 2005, at 13:16:52
In reply to The influence of the pharmaceutical industry, posted by ed_uk on February 18, 2005, at 10:01:19
I think everyone, especially everyone who posts on this board, should read MAD IN AMERICA. In the few published reviews it got, it was totally trashed by dogmatic psychiatrists like E. Fuller Torrey (the STAUNCH advocate of making it easier to hospitalize people against their will in the US)...that said, the data is sound (in addition to my sociology major, I do a lot statistics in college right now, so I checked this stuff out) and the information is AMAZING...for instance:
1) The FDA has PROHIBITED the Risperdal people from advertising their product as superior to older drugs. Why? THe comparison studies were highly flawed, using excessive amounts of Haldol (known to cause all kinds of problems) as a control. Of all the "atypicals," available data seems to suggest the Risperdal is the most likely to cause EPS and tardive dyskinesia.
2) Lobotomy is back! "Refined" versions of brain hacking (ummm..."neurosurgery") popped up in the late 40s, early 50s...with the fall of lobotomy, these "targeted" procedures, which often involve burning lesions into brain tissue, have been used on a very small number of patients in the US and an untold number abroad.
Really, its an awesome book.
Posted by ed_uk on February 18, 2005, at 13:56:21
In reply to Re: The influence of the pharmaceutical industry, posted by med_empowered on February 18, 2005, at 13:16:52
Hi med!
>The comparison studies were highly flawed, using excessive amounts of Haldol.
Yes, all the comparison studies I've seen have used vastly excessive doses of Haldol. Haldol would be a lot less vile if patient's weren't so commonly overdosed on it!
Ed.
Posted by Phillipa on February 18, 2005, at 14:08:37
In reply to Re: The influence of the pharmaceutical industry » med_empowered, posted by ed_uk on February 18, 2005, at 13:56:21
All I know is that when an elderly pt experienced confusion at night, and became combative or yelled out, they were given haldol. They kept giving it to them until they passed out. Then they slept for days. I hate this drug. Fondly, Phillipa
Posted by ed_uk on February 18, 2005, at 14:55:11
In reply to Re: The influence of the pharmaceutical industry, posted by Phillipa on February 18, 2005, at 14:08:37
Yes, it is common to OD people on Haldol, single doses of 5-20mg are often given to vulnerable patients who would probably do better on 0.5mg. No other antipsychotic has been so routinely prescribed in vastly excessive doses.
Ed.
Posted by banga on February 18, 2005, at 17:56:03
In reply to Re: The influence of the pharmaceutical industry, posted by ed_uk on February 18, 2005, at 14:55:11
Data is SO easy to manipulate. Don't like the result you got using one analysis? Use a different type, subdivide your subject groups differently, don't report it.
Studies should be examined by persons looking not only at the design, subject demographics, etc., but also with an assumption that the researcher is not invested in finding a certain result--
and investigate who benefits and in what way from results being (who funds it? What is THEIR interest?)
I am always a little naive about people being so greedy that they are willing to do lots of unethical moves and hurt people in the pursuit of monetary gain or fame. I always assume that that is the rare case, the sociopaths....but money can warp an otherwise good honest person.
So in that context, it's VERY scary what such a person could do to manipulate data.
Posted by med_empowered on February 18, 2005, at 18:12:19
In reply to Re: The influence of the pharmaceutical industry, posted by banga on February 18, 2005, at 17:56:03
according to mad in america, the dosage of haldol used as control was 20mgs! Of course this caused LOTS of problems. Haldol has a terrible reputation...I've been doing research on drug treatment of mental illness, and one thing I found utterly disgusting were the deaths of children as young as 5 from neuroleptic malignancy syndrome caused by massive doses of haldol...what's probably worse is the chillingly cold and callous way its all recorded. Also, an experimental combo of lithium and haldol caused irreversible brain damage in subjects in a couple studies...rough stuff.
This is the end of the thread.
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