I would like to note the timing of doing the evaluation of the evidence.
Consider the case of head injury and corticosteroids use. Ten years
ago, as a novice resident I was looking for evidence on this topic and
a meta-analysis could not give me a definitive answer. [Alderson P,
Roberts I. BMJ 1997 Jun 28;314(7098):1855-9]. However, at that time,
this would have been level I evidence.

Consider the example below of the a large CRASH-RCT (#1) vs a
systematic review including the RCT (#2).

The RCT is much better for giving an answer than the previous and
perhaps the updated SR, but the SR still should be on level 1... don´t
you think?



1: Lancet. 2005 Jun 4-10;365(9475):1957-9.

Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous
corticosteroid in adults with head injury-outcomes at 6 months.

Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B, Fernandes J,
Gogichaisvili T, Golden N, Hartzenberg B, Husain M, Ulloa MI, Jerbi Z, Khamis H,
Komolafe E, Laloë V, Lomas G, Ludwig S, Mazairac G, Muñoz Sanchéz Mde L, Nasi L,
Olldashi F, Plunkett P, Roberts I, Sandercock P, Shakur H, Soler C, Stocker R,
Svoboda P, Trenkler S, Venkataramana NK, Wasserberg J, Yates D, Yutthakasemsunt
S; CRASH trial collaborators .

MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of
corticosteroids on death and disability after head injury. We randomly allocated
10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less,
within 8 h of injury, to a 48-h infusion of corticosteroid (methylprednisolone)
or placebo. Data at 6 months were obtained for 9673 (96.7%) patients.
The risk of
death was higher in the corticosteroid group than in the placebo group (1248
[25.7%] vs 1075 [22.3%] deaths; relative risk 1.15, 95% CI 1.07-1.24; p=0.0001),
as was the risk of death or severe disability (1828 [38.1%] vs 1728 [36.3%] dead
or severely disabled; 1.05, 0.99-1.10; p=0.079). There was no evidence that the
effect of corticosteroids differed by injury severity or time since
injury. These
results lend support to our earlier conclusion that corticosteroids
should not be
used routinely in the treatment of head injury.

Publication Types:
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15936423 [PubMed - indexed for MEDLINE]

2: Cochrane Database Syst Rev. 2005 Jan 25(1):CD000196.

Update of:
    Cochrane Database Syst Rev. 2000;(2):CD000196.

Corticosteroids for acute traumatic brain injury.

Alderson P, Roberts I.

UK Cochrane Centre, NHS R&D Programme, Summertown Pavilion, Middle Way, Oxford,
UK, OX2 7LG. [log in to unmask]

BACKGROUND: Traumatic brain injury is a leading cause of death and disability.
Corticosteroids have been widely used in treating people with traumatic brain
injury. OBJECTIVES: To quantify the effectiveness and safety of corticosteroids
in the treatment of acute traumatic brain injury. SEARCH STRATEGY: Electronic
sources: MEDLINE, EMBASE, Cochrane Library and specialised database searches.
Additional hand searching and contact with trialists. Date of the most recent
search October 2004. SELECTION CRITERIA: All randomised controlled trials of
corticosteroid use in acute traumatic brain injury with adequate or unclear
allocation concealment. DATA COLLECTION AND ANALYSIS: Quality of allocation
concealment was scored. Data on numbers of participants randomised, numbers lost
to follow up, length of follow up, case fatality rates, disablement, infections
and gastrointestinal bleeds were extracted independently and checked. MAIN
RESULTS: We identified 20 trials with 12303 randomised participants. The effect
of corticosteroids on the risk of death was reported in 17 included trials. Due
to significant heterogeneity we did not calculate a pooled estimate of the risk
of death. The largest trial, with about 80% of all randomised
participants, found
a significant increase in the risk ratio of death with steroids 1.18 (1.09 to
1.27). For the nine trials that reported death or severe disability, the pooled
relative risk was 1.01 (0.91 to 1.11), although this does not yet contain data
from the largest trial. For infections the pooled risk ratio from five
trials was
1.03 (0.99 to 1.07) and for the ten trials reporting gastrointestinal bleeding
1.23 (0.91 to 1.67). AUTHORS' CONCLUSIONS: In the absence of a meta-analysis, we
feel most weight should be placed on the result of the largest trial. The
increase in mortality with steroids in this trial suggest that
steroids should no
longer be routinely used in people with traumatic head injury.

Publication Types:
    Review

PMID: 15674869 [PubMed - indexed for MEDLINE]



-- 
Carlos A. Cuello-García, MD
Director, Centre for Evidence-Based Medicine-ITESM
Cochrane-ITESM coordinator. Professor of Paediatrics and Clinical Research
Avda. Morones Prieto 3000 pte. Col. Doctores. CITES 3er.
piso,Monterrey NL, México. CP64710 Phone. [+52](81)8888-2154 y 2141
www.cmbe.net

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