Re: Redback spider bites in children in South Australia: A 10‐year review of antivenom effectiveness

Dear Editor, We read with concern the study by Cocks et al. which aims to evaluate the effectiveness of redback spider antivenom (RBSAV) using a retrospective, single arm methodology. This methodology is questionable in the context of existing clinical trials, which have demonstrated RBSAV to be no better than standard analgesia alone. The authors use inconsistent approaches to assess resolution of pain post-administration of RBSAV, utilising pain scores where possible and the highly subjective clinical impression when not available. Effectiveness is reported as resolution within 2 h of RBSAV administration and also upon patient discharge. However, ED length of stay data are not provided, which combined with a lack of follow up, make any meaningful interpretation of this difficult. Pain is a significant and persistent problem in latrodectism potentially lasting up to 48 h, hence both RAVE and RAVE II randomised controlled trials reporting analgesic effect up to 24 h postadministration. Cocks et al. report 56 of 61 (92%) patients having a good response to RBSAV. However, they also report 10 of the 61 receiving antivenom required opioid analgesia for ongoing or recurrent pain. This implies that between 5 and 10 (9–18%) patients were somehow classified as having a good response to RBSAV, despite significant ongoing analgesic requirements. Another significant limitation of the present study is the absence of details regarding pain resolution in those not receiving RBSAV. This omission raises significant doubt in concluding RBSAV to be the factor resulting in clinical improvement in those receiving antivenom. Cocks et al. suggest a placebo effect to be a possible limitation of their study. In contrast, we propose this not to be a limitation, but the definitive explanation of their findings. Although not a true placebo effect, a ‘belief in the treatment’ effect is clearly demonstrated when RAVE and RAVE II studies are compared (Fig. 1). Details of effectiveness are presented for a cohort from each study receiving the same treatment and in whom the same outcomes were measured. The findings demonstrate knowledge of receiving antivenom significantly influencing outcomes in treating latrodectism, with the ‘belief’ that RBSAV was administered being twice as effective as analgesia for pain, and 2.5 times more effective for treating systemic effects. The authors also report their findings as similar to previous retrospective studies demonstrating RBSAV effectiveness, including the study by Sutherland. However, all but 44 of 2117 RBSAV administrations in Sutherland’s study were via the intramuscular (IM) route. This implies Cocks’ analysis of intravenous (IV) antivenom to be similar to IM administration by Sutherland. Conversely, the RAVE trial demonstrated no difference in effectiveness between IM and IV routes, with RBSAV undetectable in serum for up to 5 h after IM administration. The authors interpretation of the Sutherland study also appears to contradict their attribution of treatment failure in two of the five cases of RBSAV to use of the IM route. The RAVE II study did not recruit children under 8 years due to pain assessment being difficult to measure reliably in this age group. Cocks et al. use this to justify their research question but cite no plausible science to support why a treatment shown to be ineffective in those aged 8 and above, might demonstrate significantly different efficacy in those aged less than 8. Despite the inclusion of 123 (53%) cases under 8 years they provide no details as to how they dealt with the lack of a validated approach to assessment of pain in this age group. Critical analysis of their