In 1993, Cowley and his colleagues reported a controlled trial of the anti-arrhythmic drug lorcainide in heart attack (1). Nine men allocated to the drug had died compared with only man allocated placebo.
This trial had actually been completed in 1980. It was eventually reported when the authors saw that it could have provided warning of what, by then, had become crystal clear, namely, that anti-arrhythmic drugs were more likely to be lethal than helpful.
I have often used this example to emphasise the importance of publishing all well conducted trials. The Cowley report has been included in the James Lind Library (www.jameslindlibrary.org) because it is a very rare example of researchers commendably exhuming and reporting an unreported trial.
We know too little about why trials remain unreported, and care is needed in arriving at judgements about who or what is to blame (2). Because I wanted to know the story of the lorcainide trial in more detail, I asked John Hampton, senior author of the Cowley report, to write an account of the lorcainide trial story. This has been published in the James Lind Library (3), and here are some key passages from his account:
“On completing our study we tried to publish our results. Full of enthusiasm we started with The Lancet and then tried two or three cardiology journals. The result was always the same – immediate rejection.”
“At a coffee break in 1993, someone remembered our old lorcainide study and we realised that it was a perfect example of many of the failings of clinical trials. I suppose we had always felt that we had a moral duty to publish it…so we tried again, [and] again, the high-impact factor journals were not interested. It was perhaps as a final throw of the dice that we added the words ‘publication bias’ to the title, and so finally found a home for the paper.”
While continuing to press for publication of unpublished trials we need to understand better the various factors that can lead to non-publication. As it happens, many premature deaths would have been avoided had more attention been paid (4) to systematic reviews of trials of anti-arrhythmic drugs published in the late 1980s (5, 6). Even without data from the lorcainide trial, these showed that these drugs were likely to be lethal, yet they continued to be used in practice and in further clinical trials.
Iain Chalmers, Coordinator, James Lind Initiative
1 Cowley AJ, Skene A, Stainer K, Hampton JR (1993). The effect of lorcainide on arrhythmias and survival in patients with acute myocardial infarction: an example of publication bias. International Journal of Cardiology 40:161-166.
2 Goldacre B. Bad Pharma. London: Fourth Estate, 2012, p 11.
3 Hampton J (2015). Therapeutic fashion and publication bias: the case of anti-arrhythmic drugs in heart attack. JLL Bulletin: Commentaries on the history of treatment evaluation (www.jameslindlibrary.org). http://www.jameslindlibrary.org/illustrating/articles/therapeutic-fashio...
4 Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC (1992). A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. JAMA 268:240-248.
5 MacMahon S, Collins R, Peto R, Koster RW, Yusuf S (1988). Effects of prophylactic lidocaine in suspected acute myocardial infarction. An overview of results from the randomized, controlled trials. JAMA 260:1910-6.
6 Hine LK, Laird N, Hewitt P, Chalmers TC (1989). Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Archives of Internal Medicine 149:2694-8.
Competing interests: No competing interests