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Education And Debate

Monitoring clinical trials—interim data should be publicly available

BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7310.441 (Published 25 August 2001) Cite this as: BMJ 2001;323:441

Rapid Response:

Monitoring clinical trials - interim data should not be publicly available

Richard Lilford and colleagues show little understanding of the
uncertainties involved in the assessments of treatment effects.1 Few
people are aware of how much point estimates wander about as both more
patients and longer follow-up accrue in a randomised clinical trial. This
means that choices made by patients on the basis of interim analyses is
unlikely to be 'rational'. The trouble is that when results go in a
particular direction, the natural instinct is to assume that they will
continue that way. This is why phrases appear in papers such as 'there was
a trend of 5% in favour of treatment A, but this is not yet significant',
implying that with more data it will become so. Of course, it is just as
likely that future data will add up in the other direction so that the
final result may be against treatment A.

Data monitoring committees have been implemented for good reasons
which have been well discussed in the past. The issues involved in
assessing results are not simple, and involve not only statistical
uncertainty but issues such as length of follow-up, internal consistency,
baseline comparability, compliance, adjustment for repeated tests,etc.2

The publication of interim results of ISIS2 was for a particular subgroup
where benefit was clear.3 There are obviously circumstances where report
of certain results will increase recruitment (for example, where sceptical
clinicians may decide to start entering patients due to an apparently
positive effect), and others where they will reduce it (for example, a
slightly positive result might make clinicians stop recruiting, with the
sceptical ones all stopping use of the treatment and optimistic ones all
deciding to use it).

Rather than going backwards and repeating the mistakes of the past,
where almost all trials were too small to give definite answers - and even
some of those that apparently did, later turned out to be misleading4 - we
should be concentrating on the problem of lack of reporting of final
results for all randomised trials done. At present the information
available on a question is often a biased subset due to this lack of
publication.5,6

1. Lilford RJ, Braunholtz D, Edwards S, Stevens A. Monitoring
clinical trials - interim data should be publicly available. BMJ 2001;
323:441-2.

2. DeMets DL. Data monitoring and sequential analysis - an academic
perspective. J Acquired Immune Deficiency Syndromes 1990; 3(Suppl 2):S123
-S133

3. ISIS-2 Steering Group. Intravenous streptokinase given within 0-4 hours
of onset of myocardial infarction reduced mortality in ISIS-2. Lancet
1987; i:502

4. Collins R, Peto R, Gray R, Parish S. Large-scale randomized evidence:
trials and overviews, in Oxford Testbook of Medicine (ed Weatherall DJ,
Ledingham JGG, Warrell DA) 1996; p21-32

5. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in
clinical research. Lancet 1991;337:867-72

6. Dickersin K, Min YI, Meinert CL. Factors influencing publication of
research results: follow-up of applications submitted to two institutional
research boards. JAMA 1992;263:374-8

Competing interests: No competing interests

22 September 2001
S M Richards
Senior Research Fellow
CTSU, Oxford