Methodology of clinical studies dealing with the treatment of envenomation.

A total of 142 clinical studies have been devoted to the treatment of envenomations, of which 115 address snake bites, 20 scorpion stings, and 8 other animals (one addresses both snake and spider envenomation). Antivenom use was studied in 118, of which 82 addressed efficacy, 43 evaluated safety, 23 studied dosage and 8 explored other issues. Besides anecdotal clinical reports, three classes of clinical studies are distinguished: (a) observational clinical studies (55 of the total) which analyze series of cases, (b) comparative clinical studies (36) which compare therapeutic products or treatment regimens without a gold standard for comparison and (c) randomized clinical trials (RCT, 51). The goals, methods and constraints of design of RCT are determined by whether explanatory (analytical) or pragmatic considerations are prioritized. Explanation-oriented RCT rely on strict group comparability before and during treatment, in order to ensure the internal validity of the study. The pragmatically-oriented RCT aims at establishing the superiority of a treatment over another, the goal being to maximize the external validity of the trial (that is, its application in current practice). We found that all clinical studies of treatment of envenomation lean markedly toward the explanatory end and suggest that, given some particularities of envenomation as a medical condition, a more pragmatic approach may be of value, particularly under the conditions prevalent for clinical studies in developing nations. 2010 Elsevier Ltd. All rights reserved.