Case reports of suspected adverse drug reactions

Editor—The main difference between the replications by Loke et al of Venning's studies from the 1980s and the original is the evidence that is accepted as further follow-up.¹ Loke et al mention that 56 of 63 case reports on adverse reactions were cited at least once but accept only nine instances as valid follow-up: attempts at proof of mechanisms or controlled studies. However, unexpected adverse effects are by definition due to an unknown mechanism, and many established adverse effects still escape elucidation after years. Moreover, further accumulation of anecdotal reports can be sufficient evidence. A 10 year tally of 22 drugs that were withdrawn from the market showed that 18 were prompted by case reports and only four by a controlled study; for at least 13 the case reports proved sufficient reason for withdrawal.²

A highly unusual event that is repeatedly to an exceedingly high relative risk, a good argument for cause and effect.³ Moreover, these risks will be picked up spontaneously.⁴,⁵

Figure 1.

Credit: PHOTOS.COM

Apart from the nine instances of follow-up that were accepted by Loke et al, 15 datasheets were amended and seven BNP drug monographs changed. So, even with some overlap, close to half of the case reports were somehow sufficiently noteworthy to have had consequences. Given the small sample size, this is not far from Venning's original. It is a pity that Loke et al do not make all follow-up more explicit for all 56 instances that followed the 63 reports.

Their overall conclusion that lack of follow-up means that case reports are of limited value is a non-sequitur. It shows that a more consistent scheme of hypothesis-testing studies by industry, government, or third parties is needed instead of the current haphazard approach to drug safety. Such publications may alert and help clinicians in recognising potential adverse events in their patients. Often there is no other way of discovering something unusual. The record of systematic—that is, controlled—postmarketing surveillance in detecting unexpected adverse effects remains surprisingly poor.