Healthy Skepticism Library item: 16890
Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.
Publication type: Electronic Source
Brody H
Another Example of Spin in Published Results of Industry-Sponsored Clinical Trials
Hooked: Ethics, Medicine and Pharma 2009 Nov 27
http://brodyhooked.blogspot.com/2009/11/another-example-of-spin-in-published.html
Full text:
Long-time readers of this blog may want to skip this post; but starry-eyed optimist that I am, I continue to believe that a new reader or two may show up once in a while, and so it may be worth adding further examples of how carefully you have to read published reports of clinical trials in medical journals to detect marketing spin in industry-sponsored research. I was alerted to the present study thanks to the good offices of “Primary Care Medical Abstracts,” aka Drs. Rick Bukata and Jerry Hoffman.
Tapentadol (Nucynta) is one of the newest analgesics to be discovered and tested. The article by Kleinert and colleagues claims that it is special in having two mechanisms of action—it affects the mu-opioid receptor as does morphine and the other opiates; and it also has norepinephrine-reuptake-inhibition properties. The present study was a double-blind controlled trial of a single oral dose of various medications to treat pain following extraction of a wisdom tooth. The investigators compared 5 different doses of tapentadol to 60 milligrams of morphine (a good sized dose ordinarily, but with a proviso we’ll get to in a minute); 400 milligrams of ibuprofen (two over-the-counter Motrin); and placebo.
The pain outcomes were measured using the 100-mm visual analog scale, asking people to mark on a 10-point, 100-mm line where their pain was at any given time and then measuring to the nearest mm. To interpret such a study you need to know the relationship between a statistical drop in pain and a clinically important drop in pain, when you combine the scores of many research subjects in a trial and get a numeric average. This has been looked at repeatedly and it is generally agreed that a drop in pain of 13 mm is the minimum pain relief that a patient can actually detect as a clinical response. That is, if you do a study of a drug and the result is that the drug reduced pain by 10 mm, you can say that this drug is clinically worthless as it did not reach the threshold where a patient could tell the difference.
So when Kleinert et al. report the results for their 399 subjects, the first thing it is logical to do is to compare these reuslts to the clinical threshold. It turns out that of all the doses and drugs tested, only 3 turn in a degree of pain relief on the primary outcome measure that surpasses the minimum threshold—the highest dose tested (200mg) of tapentadol (15.3), morphine (13.8), and ibuprofen (17.9). Notice that in this situation morphine just barely sneaks past the threshold limit. Dr. Hoffman suggests in his commentary that this can be explained by the rapid rate at which oral morphine is metabolized by the liver when one receives a single dose. Also note that none of these numbers is all that much over the threshold so as to make the results worth writing home about.
So how would a strictly honest scientist report these findings? The most candid report would probably be, “In this study, none of the drugs at the dosages tested produced substantial, clinically important pain relief.”
What Kleinert and colleagues reported was, first, that tapentadol was obviously better than placebo (which came in at a measly 4.7 mm); and second, that the highest dose was better than morphine. As they say in the abstract (which is all that most readers will bother to read of the article), “Pain relief scores with morphine sulfate 60 mg were between those of tapentadol HCl 100 and 200 mg….These data suggest that tapentadol is a highly effective, centrally acting analgesic…”
Now, note what they also could have said if they were reporting honestly: “The pain relief achieved with the very highest dose of tapentadol was less than what you can get with cheap over-the-counter ibuprofen 400 mg.” The way that they handled the inconvenient comparison between ibuprofen and their own drug was to finesse it out of the picture. They explained that ibuprofen, being both analgesic and anti-inflammatory, is a “gold standard” drug for treating dental-extraction pain. In their study, ibuprofen was superior to placebo. This fact, they proclaimed proudly, “established the sensitivity of the model.” It was as if the only reason they included the ibuprofen in the study was to show that their experimental model worked. The fact that ibuprofen then outperformed their own drug was conveniently ignored.
If you are interested in the details of the cost issue, I’ll report that on drugstore.com, 90 pills of 100 mg Nucynta costs $269.95, coming in at just $3.00 per tablet. Since to get the relief superior to morphine you had to take 200 mg in the study, that would be $6.00 per dose. You might walk into your local pharmacy with six bucks and see how many generic ibuprofen you can buy with that cash.
All of this reminds me of a joke from the old days during the depts of the Cold War, when Soviet propaganda often reached absurd extremes in trying to prove to the average Russian citizen that the USSR was truly better than the US. An auto race was held as match race between two vehicles only, an American and a Russian car. Thje Americans won. The race was reported in the Soviet Communist newspaper Pravda as: “The Russian car came in second. The US car finished next to last.”
Kleinert R, Lange C, Steup A, et al. Single dose efficacy of tapentadol in postsurgical dental pain: the results of a randomized, double-blind, placebo-controlled trial. Anesthesia and Analgesia 107:2048-2055, December 2008.
