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monitoring and are therefore compatible with a range of approaches that may vary depending on multiple factors. FDA’s guidance for industry Oversight of Clinical Investigations – A RiskBased Approach to Monitoring (August 2013) clarifies that sponsors can use a variety of approaches to fulfill their responsibilities for monitoring clinical investigations; the guidance also describes monitoring activities that reflect modern, risk-based approaches, including remote monitoring when appropriate. The decision as to whether remote monitoring conducted for a given site or clinical investigation was adequate or should be followed up with additional on-site monitoring visits should be based on the sponsor’s ongoing risk assessment. The sponsor may determine that on-site follow-up of remote monitoring activities is appropriate based on a risk assessment (e.g., sites with certain data anomalies or a higher frequency of errors, important protocol violations, or dropouts relative to other sites). As with on-site monitoring, remote monitoring should be focused on critical data and processes for human subject protection and trial integrity, such as the site’s conduct of key study procedures and documentation related to important efficacy endpoints and safety assessments. Ivermectin Evidence Review Update Oct 5, 2021, AHS Scientific Advisory Group The AHS Scientific Advisory Group (SAG) and the COVID-19 Therapeutics Working Group continue to monitor new evidence on ivermectin. After review there continues to be insufficient evidence of benefit, and the previous recommendations continue to be upheld: • At this time, ivermectin should not be prescribed or taken to prevent or treat COVID-19 (outside of a clinical trial, although SAG is currently not aware of ongoing trials in Alberta). The SAG and the Therapeutics Working Group will continue to monitor and assess new evidence on ivermectin as it is published. Several high quality randomized controlled trials are being conducted to further study the use of ivermectin for COVID-19; this review and recommendations will be updated as new evidence comes to light. Since the previous reviews, there were two significant updates on the evidence for ivermectin use in COVID-19 that SAG would like to comment on: 1. Guidelines and Evidence Review Update: Fraudulent Data Withdrawn A recent Cochrane systematic review by Popp et al. (July 2021) is in alignment with AHS and other jurisdictions (including the US National Institutes of Health, the World Health Organization, Health Canada, and the US Food & Drug Administration. It concludes that the reliable evidence available to date does not support the use of ivermectin for treatment or prevention of COVID19 (outside of well-designed randomized trials). The authors found that the available studies varied widely in the dosages used, the other medications included as comparators, and the outcomes examined, and that many of the studies were at high risk of bias (meaning any differences noted across groups were likely due to other factors). This Cochrane review excluded a study (Elgazzar et al.) that contributes to the positive findings noted in some other meta-analyses. It should be noted that the Elgazzar et al. RCT, which reported results that were very favorable to ivermectin, has been withdrawn from the preprint server for possible data fraud, so any reviews or meta-analyses that include it are not valid. For details on the issues identified in the Elgazzar et al. study, please see the article published in Nature (some of the issues include duplicated patient records, patients whose records indicate they died before the study started, and phrases that were identical to other published work). The SAG is aware that there has been considerable social media attention related to ivermectin as an effective therapy for COVID-19, in part due to the study by Elgazzar and meta-analyses using that study as well as other lesser quality observational trials with significant data issues including impossible numbers, unexplainable mismatches between trial registry updates and published patient demographics, and nonfeasible timelines. Given the ongoing investigation of these studies, more may be withdrawn over the coming months. Concerns regarding the lack of assessment of quality of these studies have been published, stating that “relying on low-quality or questionable studies in the current global climate presents severe and immediate harms. The enormous impact of COVID-19 and the consequent urgent need to demonstrate the clinical efficacy of new therapeutic options provides fertile ground for even poorly evidenced claims of efficacy to be amplified, both in the scientific literature and on social media. This context can lead to the rapid translation of almost any apparently favorable conclusion from a relatively weak trial or set of trials into widespread clinical practice and public policy.” 2. Commentary on Ivermectin Use in Uttar Pradesh, India Multiple social media sources have also reported that ivermectin might have been responsible for reducing COVID-19 cases in Uttar Pradesh, India, with claims that the low rate of new cases in spite of low vaccination rates in this region is related to distribution of ivermectin-containing medication kits. There are several potential issues with these lines of reasoning, including: • Both observational trial 

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