Letters

Quality of randomised controlled trials in head injury

Statistical power can be increased

More trials are needed

Statistical power can be increased

EDITORWe agree with Dickinson et al¹ that larger and better designed randomised controlled trials are necessary to detect benefits of treatment in head injury.² But increasing the sample size is not the only solution to show efficacy. The statistical power of a study can also be improved by randomising the same number of patients but taking prognostic factors, such as age or Glasgow coma scale, into account.

Firstly, one might limit the inclusion of patients to those with an intermediate prognosisfor example, between 20% and 80% probability of a favourable outcome.³ This leads to a focus on patients for whom treatment effects can be well determined. For the same power, a reduction in sample size of 30% might be achievable.³ After showing efficacy in the intermediate risk group, additional funding may be raised more easily to study patients with a poorer or better prognosis. Note that this reasoning assumes that the relative effect of a treatment is constant across risk groups. This is in contrast to the assumption of an absolute effect of 5% as discussed by Dickinson et al. Such an absolute effect is comparatively large at a baseline incidence of 20%, as indicated by an odds ratio of 0.71 for the comparison of an incidence of 15% versus 20%. In contrast, the odds ratio is 0.82 for the same absolute effect at 50% baseline incidence (45% v 50%). The absolute effect of 5% is more easily detected at a baseline incidence of 20%, while a relative effect such as an odds ratio of 0.71 is more easily detected at an incidence of 50%. So the assumption of an absolute or relative effect is crucial in reasoning about power and inclusion criteria.

Secondly, even if inclusion would be limited to patients at intermediate risk, heterogeneity will remain regarding the probability of a favourable outcome. Predictive characteristics which account for this heterogeneity can be adjusted for in the analysis, which will increase the statistical power to detect a treatment effect.⁴ In an analysis of patients with acute myocardial infarction, the potential reduction in sample size was 12% by adjustment for age.⁵

Besides dealing with heterogeneity, we may also consider restricting data collection to the essential variables, such that larger numbers of patients are accrued at the same costs. We hope that the strategies here proposed will be applied in the study of therapy for head injury, together with an increase in funding.

Chantal W P M Hukkelhoven, epidemiologist. 
hukkelhoven{at}mgz.fgg.eur.nl

Ewout W Steyerberg, epidemiologist. 
Andrew I R Maas, neurosurgeon. 
Erasmus Medical Centre Rotterdam, 3000 DR Rotterdam, Netherlands

More trials are needed

EDITORDickinson et al are to be congratulated for highlighting the deficiencies in research into head injury.¹ The situation is no better for children with head injuries. The American Academy of Pediatrics issued a report based on extensive literature review of 108 articles on head injury in children.² The academy concluded that the literature on mild head trauma does not provide a sufficient scientific basis for evidence based recommendations about most of the key issues in clinical management.

To address this issue, a multicentre study to develop a set of clinical decision rules for the management of head injured children is now in its third month of data collection. All children with head injuries at nine hospitals in the north west of England are seen by the attending doctor using a tailored study pro forma. Forty clinical correlates relating to symptoms, signs, and investigations are entered. We are collecting patients at the rate of 1300 per month. Once 15 000 forms have been collected, all data on admission, neurosurgical intervention, and mortality will be collected. A set of clinical decision rules will then be derived using recursive partitioning (as with the Ottawa ankle guidelines). The guidelines will then be validated in a further 15 000 patients.

This is the first time that such an approach has been used in the management of head injury, and I agree with Dickinson et al that it is only by large, well conducted trials that we are going to advance the evidence base in head injury

Joel Desmond, cardiothoracic senior house officer. 
Wythenshawe Hospital, Manchester M23 9LT joeldesmond{at}doctors.org.uk