Case reports of suspected adverse drug reactions—systematic literature survey of follow-up

Loke et al. judge the value of case reports of suspected adverse drug

reactions (ADR) by the outcome measures of further formal validation and
the
incorporation into the product information and conclude that such reports
are of limited value.

The principle sources of information or tools that are available for
the
detection and evaluation of ADR are spontaneous reports, formal
epidemiological studies and controlled clinical trials, plus meta-
analyses.
Misunderstandings about the value of drug safety activities regularly
occur
when inappropriate tasks or unrealistic expectations are assigned to these

tools: attempts are made to derive causal “proof” or quantitative risk
estimates from spontaneous reports, spontaneous reporting systems are
blamed because they don’t detect associations when adverse events occur
with a high background incidence, epidemiological drug safety studies are
criticized for being retrospective and non-randomized, the number of
subjects in clinical trials is too low to detect rare ADR, and meta-
analyses are
subject to publication bias. However, used and interpreted appropriately,
all
of these methods have made major contributions to drug safety (1-4).

According to Loke’s report 83% of reports had not been subjected to
further
evaluation. However, the first question is whether the majority of
clinically
relevant ADR are initially communicated by case reports, and whether this
process is efficient. In other words, sensitivity combined with low cost
is the
primary concern with spontaneous reports.

In contrast to many reports of limited quality and relevance that end
up
being buried in spontaneous reports databases, published case reports of
ADR undergo peer-review for quality and relevance and are accessible to
anyone caring about drug safety. They increase specific as well as general

awareness of adverse drug effects and therefore their diagnosis in
clinical
practice, they contribute to mechanistic hypotheses, and they provide
important information for the design and conduct of formal safety studies;

and they miraculously do all this at no cost and are therefore highly
efficient.

Yes, in rare instances case reports do more harm than good, but
further
evaluations are able to identify such false signals or otherwise confirm
and
quantify safety problems (5). In their discussion, Loke et al. therefore
make
the important point that efforts should be intensified to further follow
safety
signals by formal safety studies, and that much of the considerable
resources
spent on spontaneous reporting systems may be better shifted towards such
activities. However, published case reports remain a valid and efficient
source
for signal generation and are of great value for drug safety. From that
point
of view it would be unfortunate if Loke's report
discouraged the publication of ADR.

1. Arnaiz JA, Carne X, Riba N, Codina C, Ribas J, Trilla A. The use
of evidence
in pharmacovigilance. Case reports as the reference source for drug
withdrawals. Eur J Clin Pharmacol 2001;57(1):89-91.

2. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan
K, et al.
Cardiovascular events associated with rofecoxib in a colorectal adenoma
chemoprevention trial. N Engl J Med 2005;352(11):1092-102.

3. Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal
behaviors.
JAMA 2004;292(3):338-43.

4. Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M.
Risk of
cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet
2004;364(9450):2021-9.

5. Jick H, Kaye JA. Epidemiology and possible causes of autism.
Pharmacotherapy 2003;23(12):1524-30.

Competing interests:
None declared