Faulty Study Design Produces an Outcome That May Confuse Medical Fraternity: A Serious Publication Bias
I want to raise 3 issues with the recently published study and meta-analysis of Turan et al1 relating to the study design, selective meta-analysis, and the over-reaching statement of conclusions. Study design: The study as designed was unlikely to show the benefits of clonidine. The dose of oral clonidine used for preemptive analgesia is much less than used in previous studies that found it effective.2 The oral route with its erratic absorption in the preoperative setting is more likely than the intravenous (IV) route to produce an inferior outcome. The next major fault in the design was the use of transdermal (transdermal therapeutic system [TTS]) clonidine rather than the parenteral route to treat acute postoperative pain. It is very well known that TTS system does deliver a fixed amount of drug that may or may not be sufficient to treat or reduce the widely variable severe postoperative pain. The use of a TTS patch for the treatment of immediate postoperative pain is not a rational choice because of the wide variation in pain perception and analgesic requirements. Recent studies are promising only with iontophoretic system. The authors did not mention clearly about which type of TTS patch was used. Even with iontophoretic TTS, the result is unlikely to be as effective as the IV route. I feel that, to assess the real efficacy, in both the cases the IV route should have been used. Moreover, clonidine is known only to be an alternative analgesic rather than first-line one. Solely using it in immediate postoperative pain is not a good idea. Finally, not standardizing surgery led to a huge variation in the amount of postoperative pain. Thus, verbal response scores and analgesic consumption are bound to vary and affect the outcome. Selective meta-analysis: The authors clearly debunked the concept of any role of clonidine in acute postoperative pain. But many meta-analyses including the Cochrane Review by Lambert et al2 found definite reduction in acute postoperative pain and total opioid consumption at least in the first 24 hours.2–4 Over-reaching statement of conclusions: The title of their article and the summary paragraph overstate their conclusions with a blanket condemnation of clonidine. Rather, they should have concluded that oral clonidine (0.2 mg) and TTS clonidine are ineffective in reducing postoperative pain. Their general statement is completely misleading about a well-proven drug having very good analgesic efficacy in various other routes.
I think that, before putting out such a negative statement about clonidine, it should be reevaluated using proper doses and the proper routes of administration.