Is Off-Label Usage Off Limits?

By Anthony Rosner, PhD, LLD [Hon.], LLC

When is a therapy not formally a therapy? You might answer,"When it is used for purposes other than which it was originally intended." This has brought chiropractors more than their fair share of slings, arrows and anything else that might be considered a destructive projectile when it is revealed; for instance, that spinal manipulation has been employed for managing conditions that might not seem to have the slightest kinship to the tried-and-true garden variety of ailments lumped under the terminology "low back pain." Even extending chiropractic care into such conditions as headache or extremity disorders has raised eyebrows, if not hackles, on the part of far too many detractors.

Consider how many might go ballistic at hearing at such prospects as treating colic or ear infections: Despite chiropractic complication rates that are orders of magnitude lower than death rates attributable to NSAIDs or back surgery,^1,2 there are some who go so far as to recommend a nuclear option of sorts - the outright banning of all forms of cervical manipulation.

As I pointed out in this column space some months ago,³ treating headaches by manipulation, for example, is considered taboo by the National Guideline Clearinghouse Paper on Headaches. The argument was that "the scientific evidence is not convincing."⁴ Not convincing? Is this to be taken as an argument against applying manipulation for the treatment of headaches - despite a liberal helping of systematic literature reviews that support it?^5-10 How about if we were to sashay across the aisle for a moment and consider, for comparison's sake, what is going on in standard, allopathic medicine? Consider, for a moment, the very recent publication in the Archives of Internal Medicine, which reported some 150 million citations of off-label uses of 160 drugs taken from the 2001 National Disease and Therapeutic Index. You may be dumbfounded to find that no less than 73 percent of these scrips "had little or no scientific support."¹¹ So, let me get this straight: Without scientific support, it is verboten when it's spinal manipulation, and kudos (or at the very worst, a wink and a nudge) when it's medication?

The sample taken in this study was probably no fluke, as it represented 56 percent of all estimated drug prescriptions in 2001. By way of a footnote, it turns out that just two classes of drugs (cardiac medications and anticonvulsants) represented nearly half of all off-label recommendations. Understandably, the authors of this study lodged a plea that efforts should be made to scrutinize this practice in terms of both safety and expense.¹¹
It gets worse: In 2004, the manufacturer of gabapentin (one of the anticonvulsants) was found guilty of criminal fraud for the inappropriate marketing of off-label uses of this drug.¹² And worse still: According to an estimate by the news service Knight-Ridder, from a 2003 investigation, physicians wrote up to 115 million off-label prescriptions per year, not terribly far from the 2001 estimate quoted previously.¹¹ Some 45 medications were reviewed, with off-label sales of $12.9 billion, accounting for nearly a quarter of these drugs' retail sales. Knight-Ridder estimated that anywhere between 8,000 and 80,000 people may suffer "serious adverse reactions" as a result of this activity.¹³

Regrettably, the Archives of Internal Medicine study may have shown us that practice patterns have strayed from the qualified endorsement of off-label drug usage, offered by none other than the American Medical Association:

"The AMA confirms its strong support for the autonomous clinical decision-making authority of a physician and that a physician may lawfully use an FDA-approved drug product or medical device for an unlabeled indication when such use is based upon sound scientific evidence and sound medical advice"¹⁴ (italics mine).

The fact that only 27 percent or less of the off-label usage of drugs is based upon such "sound scientific evidence," according to the Radley paper,¹¹ suggests that a strong recommendation from America's premier political medical organization has been violated. Has the AMA interceded? It would not appear so, at least through March of 2005, if you were to listen to the testimony of a member of the AMA Board of Trustees (Cecil Wilson) before the U.S. Senate Committee on Health, Education and Pensions regarding drug safety recommendations. He said the FDA should "ensure that physicians' ability to prescribe drugs off-label not be impeded."¹⁵

There are two very simple messages we can carry away from this story:

1. Restrictions on the number of conditions and areas that might be treated by chiropractic intervention, as long as such treatment appears to be safe, effective and economical, can be judged to be arbitrary and Draconian - to say nothing of hypocritical - in light of the widespread and potentially dangerous practice of off-label drug use.
   
2. The basis for escaping this dilemma and remaining in conformity with such recommendations as issued by the AMA - whether they apply to medication use, manipulation, or any therapeutic application, for that matter - is the presence of reasonably sound scientific evidence. The only means by which such evidence can be obtained, of course, is through research. And for the chiropractic community, in particular, that would most logically point to the Foundation for Chiropractic Education and Research, as the oldest and largest nonprofit venue through which both research and postgraduate study has been supported worldwide throughout its 62-year history.

It is obvious, then, that scientific evidence remains the key by which patients should be afforded any form of health care. In the absence of such evidence, as David Sackett¹⁶ and others have argued, sound clinical judgment must prevail so that parity remains among health care modalities available to the patient. The glaring fact, for which there is no justification, unfortunately remains: Off-label use of medications remains relatively unchecked while the chiropractic management of many conditions, other than back pain and possibly headache, remains off-limits.

References

1. Rosner A. CVA Risks in perspective. Manuelle Medizin 2003;3:1-9.
2. Rome PL. Perspective: an overview of comparative considerations of cerebrovascular accidents. Chiropractic Journal of Australia 1999;29(3):87-102.
3. Rosner A. "Research for Sanity and Survival." Dynamic Chiropractic, May 8, 2006.
4. Diagnosis and Treatment of Headache. Bloomington, MN: Institute for Clinical Systems Improvement [ICSI], January 2006.
5. Hurwitz EL, Aker PD, Adams AH, Meeker WC, Shekelle PG. Manipulation and mobilization of the cervical spine: a systematic review of the literature. Spine 1996;21(15):1746-1760.
6. Boline P, Kassak K, Bronfort G, Nelson C, Anderson AV. Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial. Journal of Manipulative and Physiological Therapeutics 1995;18(3):148-154.
7. Kjellman GV, Skagren EI, Oberg BE. A critical analysis of randomised clinical trials on neck pain and treatment efficacy: a review of the literature. Scandinavian Journal of Rehabilitative Medicine 1999;31:139-152.
8. Bronfort G, Assendelft WJJ, Evans R, Haas M, Bouter L. Efficacy of spinal manipulation for chronic headaches: a systematic review. Journal of Manipulative and Physiological Therapeutics 2001;24(7):457-466.
9. Vernon H, McDermaid CS, Hagino C. Systematic review of randomized clinical trials of complementary/alternative therapies in the treatment of tension-type and cervicogenic headache. Complementary Therapies in Medicine 1999;7:142-155.
10. McCrory DC, Penzien DB, Hasselblad V, Gray RN. Evidence Report: Behavioral and Physical Treatments for Tension-Type and Cervicogenic Headache. Des Moines, IA: Foundation for Chiropractic Education and Research, 2001.
11. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among off-based physicians. Archives of Internal Medicine 2006;166:1021-1026.
12. Larkin M. Warner-Lambert found guilty of promoting Neurontin off label. Lancet Neurology 2004;3:387.
13. "Risky RX: A Knight-Ridder Investigation.".
14. American Medical Association policy #H.120-988: "Patient Access in Treatments Prescribed by Their Physicians." Available at www.ama-assn.org.
15. "AMA Testifies at Senate Drug Hearing." March 3, 2005.
16. Sackett DL. Evidence-based medicine [Editorial]. Spine 1998;23(10):1085-1086.

---

Click here for more information about Anthony Rosner, PhD, LLD [Hon.], LLC.