I would like to add to Lenzer and Brownlee’s reporting of my comments on how excessively closed science can hurt physicians and patients.1
Statistician Michael Bracken led the NASCIS 2 and 3 studies of high dose steroids in acute spinal cord injury.2 The National Institute of Neurological Disorders and Stroke conducted a public campaign in advance of the scientific publication of NASCIS 2 on 17 May 1990. The institute sent a fax on 13 April 1990 to some 19 000 emergency room physicians and hospitals, after a press release had resulted in coverage by the New York Times and the Chicago Tribune on 31 March 1990, by Science News on 7 April 1990, by Newsweek on 9 April 1990.
This led to widespread use of steroids, off label. No application for regulatory approval for this indication was completed, and no agency ever approved it. Surgeons report that methylprednisolone is administered from fear of litigation, not belief in efficacy.3 Bracken reinforced this fear by testifying against physicians; he was deposed on 9 June 1998 in Civil Action File No 96A-7768-6, Superior Court of Fulton County, GA.
We have criticised NASCIS science.4 The later guidelines for the management of acute cervical spine and spinal cord injuries from the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS)5 rated the NASCIS publications as evidence class III, citing flaws in study design, data presentation, interpretation, and analysis. They listed steroid treatment only as an “option.”
The lack of demonstrated benefit must be weighed against documented risks. The CRASH trial showed a 3% greater mortality when corticosteroids were given to a multitrauma group with head injury.6 If this increased death rate held in SCI, then 5000 extra patients may have died in the US since 1990.
Yet it’s difficult to stop the momentum—especially when primary data are unavailable for independent review.
Competing interests: None declared.
References
- 1.Lenzer J, Brownlee S. Antidepressants. An untold story? BMJ 2008;336:532 (8 March.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, Eisenberg HM, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study. N Engl J Med 1990;322:1405-11. [DOI] [PubMed] [Google Scholar]
- 3.Eck JC, Nachtigall D, Humphreys SC, Hodges SD. Questionnaire survey of spine surgeons on the use of methylprednisolone for acute spinal cord injury. Spine 2006;31:E250-253. [DOI] [PubMed] [Google Scholar]
- 4.Coleman WP, Benzel E, Cahill DW, Ducker T, Geisler F, Green B, et al. A Critical appraisal of the reporting of the NASCIS II and III studies of MPSS in acute spinal cord injury. J Spinal Disord 2000;13:185-99. [DOI] [PubMed] [Google Scholar]
- 5.Hadley MN, Walters BC. Pharmacological therapy after acute cervical spinal cord injury. In: Guidelines for the management of acute cervical spine and spinal cord injuries. Neurosurgery 2002;50:S63-S72. [DOI] [PubMed] [Google Scholar]
- 6.Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 2005;365:1957-9. [DOI] [PubMed] [Google Scholar]