Use of off label drugs

Britt Smith posted on the tricky (some like to substitute illegal) marketing stategies of pharmaceutical companies promoting uses for medications that have not been approved by the FDA.  Even John Childs got in on the action with a reference in his post yesterday.  The practice of "Off Label" drug prescription is relatively common and there is a letter to the editor in July's Anesthesia and Analgesia that I thought may shed a llittle light on the subject.  Broadman LM, Semenov I. The Use of “Off-Label” Drugs. Anesth Analg. 2006; 103(1): 250-251.

Perhaps, the most classic case of off-label use of an anesthetic is the millions of times per year that caudal/epidural bupivacaine is safely and effectively used to perform spinal blocks, even though the package warns “NOT FOR SPINAL ANESTHESIA.” This is a prime example that off-label use does not necessarily mean unsafe.

This logic is very true in the case of gabapentin, the medication implicated by Dr. Rowlingson in his editorial. If it had not been for the off-label use of gabapentin by the Mellick brothers (4) for reflex sympathetic dystrophy in 1997, we would have lost access to what has become the first-line drug in the management of neuropathies associated with diabetes (5), Acquired Immune Deficiency Syndrome (6), and Guillain-Barre syndrome (7). The most recent use of gabapentin by Dr. Pandey et al. (8,9), in which gabapentin administered by mouth in a single dose on the evening prior to surgery reduced the need for narcotic analgesics by 50% in the postoperative period, provides hope that similar results can be obtained in children undergoing scoliosis surgery and other painful orthopedic procedures. In our experience, the only adverse side effect one observes with gabapentin is somnolence, a potentially beneficial side effect of a premedication.

Also I wanted to point out that there is evidence for using Anticonvulsant drugs for acute and chronic pain as indicated in this Cochrane Review.  An interesting contribution to the background of the review is that "Anticonvulsant drugs have been used in pain management since the 1960s, very soon after they were first used in medicine and revolutionised the medical management of epilepsy." 

Dan

Full disclosure: My wife is a pharmacist and although I have not been paid by "Big Pharma" for this post, the salary that my wife brings home is a substantial portion of our family's gross income.

Comments

[britt]

Dan,
Great points about the potential benefits from the 'off-shelf' use of a drug; however, it still stands as ILLEGAL to promote a use of a drug that has not been approved for that use. The onus on 'Big Pharma' is again to do the proper trials, conducted with proper protocols and transparency, that demonstrate effectiveness and seek FDA approval for that use. The EBHC conference included Drummond Rennie MD (deputy editor of JAMA) and Curt Furberg MD, PhD, who have suggested that the pharmaceutical industry is about to bring down all of medical science, for the reason Selena noted, "What can you trust?"
Cheers,
Britt

[Rob Landel]

The part of this that is disturbing to me is the use of "research" in the marketing scheme. Many journals do have a "Conflict of Interest" disclosure, but many do not. (I note that Phys Ther and JOSPT do *not* provide such a statement). How would I know if the company that makes the ultrasound unit paid for the research into its effect on fracture healing in rats (Warden et al. 86 (8): 1118. (2006))?

What's more disturbing is that while it appears appropriate to villify Big Pharma (and, I would argue, BP makes an easy target), let's not forget that academicians accepted payment for services such as serving as experts for CME, performing trials, publishing letters to the editors, presenting at conferences, and so on. The marketing strategy centered around getting "experts," "local champions," “thought leaders,” “key influencers,” and “movers and shakers,” including "current or future department chairs, vice chairs, and directors of academic clinical programs or divisions" to participate in their activities.

Now, I have no gripe against private industry funding legitimate research through competitive grant funding as long as complete disclosure is made and conflicts of interest are defined. But let's face it: this marketing strategy would not have worked without the acquiescence of those with influence, who bear at least a third of the blame (BP, the Temptor; Experts, the consenting; and Consumer, caveat emptor).

I leave you with a quote from David Sackett in his final writing about EBM, from what I consider to be Required Reading for anyone who haunts this website:

“It then dawned on me that experts like me commit... sins that retard the advance of science and harm the young. Firstly, adding our prestige to our opinions gives the latter far greater persuasive power than they deserve on scientific grounds alone. Whether through deference, fear, or respect, others tend not to challenge them, and... new ideas and new investigators are thwarted by experts, and progress toward the truth is slowed.

“Is redemption possible for the sins of expertness? The only one I know that works requires the systematic retirement of experts. To be sure, many of them are sucked into chairs, deanships, vice presidencies, and other black holes in which they are unlikely to influence the progress of science or anything else for that matter. Surely a lot more people could retire from their fields and turn their intelligence, imagination, and methodological acumen to new problem areas where, having shed most of their prestige and with no prior personal pronouncements to defend, they could enjoy the liberty to argue new evidence and ideas on the latter's merits.

“But there are still far more experts around than is healthy for the advancement of science. Because their voluntary retirement does not seem to be any more frequent in 2000 than it was in 1980, I repeat my proposal that the retirement of experts be made compulsory at the point of their academic promotion and tenure.”

Sackett DL. The sins of expertness and a proposal for redemption BMJ 2000;320:1283 ( 6 May )

In the interests of Full Disclosure: I am an academician (but thankfully not an Expert); I subscribe to, support and endeavor to practice EBP; and I buy my meds from BP.