Article type
Year
Abstract
Background: Many adverse drug reactions are first reported anecdotally and therefore require formal verification, although a minority are actually verified1. We propose that there are adverse drug reactions (we call them between-the-eyes reactions) that are so convincing that only one anecdotal report or at most a handful of reports, is necessary to provide convincing evidence of the association between the observed event and the drug with which it is associated.
Results: We have identified four categories of such reactions, based on specific criteria, which could serve as evidential gold standards, or at least very high-grade ore.
- Extrinsic or intrinsic tissue deposition of the drug or a metabolite;
- A specific anatomical location or pattern of injury;
- Physiological dysfunction or direct tissue damage, individually demonstrable by physicochemical testing;
- Infection, due either to the administration of an infective agent as the therapeutic substance or to demonstrable contamination.
Examples, of which we have so far identified about 25 types attributable to about 50 drugs, are as follows:
- Urinary calculi containing the drug in a concentration above its solubility limit (for example triamterene);
- Extravasation reactions to cytostatic drugs;
- Photosensitivity (for example to carbamazepine);
- BCGitis in patients given BCG immunization.
Conclusions: This analysis introduces a new perspective on anecdotal reports, since the criteria we propose are predicated on types of scientific evaluation that are not emphasized in most causality assessment procedures, which tend to emphasize chronological characteristics of reported associations (i.e. the time courses of challenge, dechallenge, and rechallenge). Between-the-eyes adverse reactions could be used as gold standards for assessing the quality of systematic reviews of adverse drug reactions and the methods used to perform them.
References
1. Loke YK, Price D, Derry S, Aronson JK. Case reports of suspected adverse drug reactions - systematic literature survey of follow-up. BMJ 2006; 332:335-9.
Results: We have identified four categories of such reactions, based on specific criteria, which could serve as evidential gold standards, or at least very high-grade ore.
- Extrinsic or intrinsic tissue deposition of the drug or a metabolite;
- A specific anatomical location or pattern of injury;
- Physiological dysfunction or direct tissue damage, individually demonstrable by physicochemical testing;
- Infection, due either to the administration of an infective agent as the therapeutic substance or to demonstrable contamination.
Examples, of which we have so far identified about 25 types attributable to about 50 drugs, are as follows:
- Urinary calculi containing the drug in a concentration above its solubility limit (for example triamterene);
- Extravasation reactions to cytostatic drugs;
- Photosensitivity (for example to carbamazepine);
- BCGitis in patients given BCG immunization.
Conclusions: This analysis introduces a new perspective on anecdotal reports, since the criteria we propose are predicated on types of scientific evaluation that are not emphasized in most causality assessment procedures, which tend to emphasize chronological characteristics of reported associations (i.e. the time courses of challenge, dechallenge, and rechallenge). Between-the-eyes adverse reactions could be used as gold standards for assessing the quality of systematic reviews of adverse drug reactions and the methods used to perform them.
References
1. Loke YK, Price D, Derry S, Aronson JK. Case reports of suspected adverse drug reactions - systematic literature survey of follow-up. BMJ 2006; 332:335-9.