Testimony before the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee

Meeting on Epidural Steroid Injections (ESI) and the Risk of Serious Neurologic Adverse
Reactions

Sarah Sorscher, J.D./M.P.H.

Public Citizen’s Health Research Group
November 24, 2014

Thank you and good afternoon.

I am Sarah Sorscher, a researcher speaking on behalf of myself and Public Citizen’s Health
Research Group (HRG), a consumer organization with over 40 years of research-based advocacy
for drug and medical device safety. I have no financial conflicts of interest.

Public Citizen urges this committee to recommend that the Food and Drug Administration
(FDA) require a boxed warning and contraindication against the use of steroids for epidural
injection, based on the fact that there is a class-wide risk of rare but catastrophic adverse events
that cannot be eliminated through current mitigation strategies. This risk far outweighs any
limited benefits of such injections.

Existing literature on the efficacy of epidural steroid injections suffers from a number of
shortcomings common to published research, which generally lacks many of the quality
safeguards required in data submitted to the FDA as part of a new drug approval application.

In addition, the studies of efficacy lack consistency and replicability. As stated by the FDA in its
briefing material, while numerous clinical trials have been reported in the literature, “the findings
are often mixed and comparisons are difficult to make due to differences in trial designs.”1

Bias also plays a potentially significant role. In one recent review, the medical specialty of the
investigator or reviewer was found to have a strong influence on the findings of the study or
review, with publications by pain physicians about three times more likely to report a positive
result compared to those conducted by non-pain physicians.2

1
FDA Briefing Document: Anesthetic and Analgesic Drug Products Advisory
Committee Meeting (Epidural Steroid Injections (ESI) and the Risk of Serious Neurologic Adverse Reactions).
November 24-25, 2014. p 20.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalges
icDrugProductsAdvisoryCommittee/UCM422692.pdf. Accessed November 20, 2014. [hereinafter: “FDA Briefing
Document”]
2
Cohen SP, Bicket MC, Jamison D, Wilkinson I, Rathmell JP, Epidural steroids: a comprehensive, evidence-based
review. Reg Anesth Pain Med 2013;38:175-200.
Use of steroid injections is enormously widespread despite lack of clear evidence of benefit, with
over 6.6 million injections administered over the past 5 years in the Medicare 65-and-older
population alone.3 It is not surprising that physicians who have engaged for years in such a
widespread practice, and who also derive financial benefit from the procedure, may be unable to
objectively evaluate the available evidence supporting its efficacy.

Even looking at the strongest available evidence, epidural steroid injections appear to provide
small clinical benefit. This point was well-demonstrated in a 2012 meta-analysis of epidural
steroid injections for sciatica that involved 23 randomized, placebo-controlled trials. 4 Steroid
injections were effective at preventing leg pain and disability in the short term, but were not
effective for back pain, or for long term leg pain or disability. Importantly, even the short-term
effects were small: on a scale of 0 to 100, with 0 representing no pain or disability and 100
representing worst possible pain or disability, the average effect was just 6 points for short-term
leg pain and 3 points for short-term disability, an improvement with questionable clinical
significance.5

Weighing against this dubious benefit is the risk of rare but potentially catastrophic adverse
events: death, paralysis, stroke, blindness, seizures, bowel and bladder dysfunction, and
behavioral changes, as well as arachnoiditis, possibly due to accidental intrathecal
administration.6

It is hypothesized that some of these injuries, which have not been detected with other epidural
drugs,7 are due to embolization of the particulate steroid, which may be unintentionally injected
intravascularly.8 Various mitigation strategies have been proposed, including use of so-called
“non-particulate” steroids, imaging to prevent vascular penetration, use of supposedly safer
routes of administration, and use of a blunted needle.9

None of these strategies appears to eliminate the risk of catastrophic injury.

It is clear from adverse event data and case reports that while catastrophic neurological injuries
are more commonly reported using particulate steroids, injuries have also occurred with non-
particulate steroids, indicating that the risk is class-wide.10 Relative use rates have not, to our
knowledge, been studied, making it impossible to draw conclusions based on the raw number of
reported adverse events. A study in rats conducted by Dawley et al revealed that extensive

3
FDA Briefing Document at 56.
4
Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the management of sciatica. Ann
Intern Med 2012; 157:865-877.
5
Ibid.
6
FDA Briefing Document at 52, 84, 93.
7
Ibid. at 159, 164.
8
Dawley J, Moeller-Bertram T, Wallace MS, Patel P, Intra-arterial injection in the rat brain: Evaluation of steroid
used for transforaminal epidurals. Spine 2009;34(16):1638-1643.
9
FDA Briefing Document at 89-92.
10
FDA Briefing Document at 52.
neurological damage could be caused by both particulate and non-particulate formulations of
methylprednisolone.11

Imaging also cannot fully prevent accidental intravascular injection or adverse events. One study
of over 500 transforaminal cervical injections reported a rate of intravascular injection
approaching 20%, despite the use of fluoroscopy.12 Looking at adverse event data and published
reports, catastrophic injuries have occurred despite use of multiple types of imaging. 13,14

Similarly, catastrophic neurological injuries have been reported with every route of epidural
administration, including the interlaminar and caudal approaches, which are generally thought to
be the safest.15,16 Likewise a risk of accidental intravascular injection may remain present even
with use of a blunt needle.17

Epidural steroid injections offer dubious benefits and present risks of life-threatening and
disabling harm that cannot be eliminated through currently proposed mitigation strategies. Such
risks clearly warrant a boxed warning and contraindication.

Patients should not be expected to submit to the chance, however slight, of fatal or disabling
injury in exchange for the unvalidated, clinically questionable, short-term benefit of 6 points
improvement on a hundred-point pain scale. To prevent this, both patients and physicians should
be clearly informed of these risks in the product labeling.

Thank you for your time today.

11
Dawley J, Moeller-Bertram T, Wallace MS, Patel P, Intra-arterial injection in the rat brain: Evaluation of steroid
used for transforaminal epidurals. Spine 2009;34(16):1638-1643.
12
Furman MB, Giovanniello MT, O’Brien EM, Incidence of intravascular penetration in transforaminal cervical
epidural steroid injections. Spine 2003;28:21-25.
13
FDA Briefing Document at 84.
14
Popescu A, Lai D, Lu A, Gardner K, Stroke following epidural injections—case report and review of literature. J
Neuroimaging 2013;23:118-121.
15
FDA Briefing Document at 90.
16
Ibid.
17
Ibid at 91-92.