Opioids in the United Kingdom: safety and surveillance during COVID-19.

PURPOSE OF REVIEW: Opioid use is prevalent in the United Kingdom and prior to the COVID-19 pandemic it had been recognized that the safety of opioids was an important issue to be monitored by the UK medicines regulatory agency. With the emergence of COVID-19, this requirement has been even greater. This review was undertaken to determine the impact of the pandemic on safety and surveillance of opioids in the United Kingdom. RECENT FINDINGS: During the COVID-19 pandemic, the surveillance of opioids in the United Kingdom continued, although primary research was often conducted with data prior to the pandemic. Of those studies that were conducted while the pandemic was ongoing, access to opioids (or opioid substitution therapy) and the subsequent effect on patient safety was the main theme. SUMMARY: In the United Kingdom, changes in accessibility to the healthcare system and how healthcare providers operated during the COVID-19 pandemic may have had unintended consequences on use and safety of opioids, due to the shift in focus to preventing COVID-19 from overwhelming the healthcare system. The findings from this review support the need to continue surveillance in the United Kingdom, including the impact of the COVID-19 pandemic on opioid utilization and safety.

Postmarketing studies: can they provide a safety net for COVID-19 vaccines in the UK?

In the current era of the COVID-19 pandemic, the world has never been more interested in the process of vaccine development. While researchers across the globe race to find an effective yet safe vaccine to protect populations from the newly emergent SARS-CoV-2 virus, more than one-third of the world has been subjected to either full or partial lockdown measures. With communities having felt the burden of prolonged isolation, finding a safe and efficacious vaccine will yield direct beneficial effects on protecting against COVID-19 morbidity and mortality and help relieve the psychological and economic load on communities living with COVID-19. There is hope that with the extraordinary efforts of scientists a vaccine will become available. However, given the global public health crisis, development of a COVID-19 vaccine will need to be fast tracked through the usual prelicensing development stages and introduced with limited clinical trial data compared with those vaccines that are developed conventionally over more than a decade. In this scenario, surveillance of the vaccine in the real world becomes even more paramount. This responsibility falls to observational researchers who can provide an essential safety net by continuing to monitor the effectiveness and safety of a COVID-19 vaccine after licensing. Postauthorisation observational studies for safety and effectiveness are complementary to prelaunch clinical trials and not a replacement. In this paper, we highlight the importance of postmarketing studies for future newly licensed COVID-19 vaccines and the key epidemiological considerations.

Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment.

INTRODUCTION AND OBJECTIVE: COVID-19 is an ongoing, global public health crisis for which safe and effective treatments need to be identified. The benefit-risk balance for the use of lopinavir-ritonavir in COVID-19 needs to be monitored on an ongoing basis, therefore a systematic benefit-risk assessment was designed and conducted. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation; although initially this evaluation is likely to contain limited information, it is required because of the urgent unmet public need. Importantly, it allows additional data to be incorporated as they become available, and re-evaluation of the benefit-risk profile. METHODS: A systematic benefit-risk assessment was conducted using the Benefit-Risk Action Team (BRAT) framework. The exposure of interest was lopinavir-ritonavir treatment in severe COVID-19 compared to standard of care, placebo or other treatments. A literature search was conducted in PubMed and Embase to identify peer-reviewed papers reporting clinical outcomes. Two clinicians constructed a value tree and ranked key benefits and risks in order of considered clinical importance. RESULTS: We screened 143 papers from PubMed and 264 papers from Embase for lopinavir-ritonavir; seven papers were included in the final benefit-risk assessment. In comparison to standard of care, data for several key benefits and risks were identified for lopinavir-ritonavir. Time to clinical improvement was not significantly different for lopinavir-ritonavir in comparison to standard of care (hazard ratio 1.31, 95% confidence interval 0.95-1.80). From one study, there were fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard of care (13% vs 27%). There also appeared to be fewer serious adverse events with lopinavir-ritonavir (20%) vs standard of care (32%). Limited data were available for comparison of lopinavir-ritonavir to other treatments. CONCLUSIONS: Based on currently available data, there was no clear benefit for the use of lopinavir-ritonavir compared to standard of care in severe COVID-19. Risk data suggested a possible decrease in serious adverse events. There was a reduction in acute respiratory distress syndrome with lopinavir-ritonavir in one study. Overall, the benefit-risk profile for lopinavir-ritonavir in severe COVID-19 cannot be considered positive until further efficacy and effectiveness data become available.

Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment.

INTRODUCTION: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. METHODS: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. RESULTS: Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). CONCLUSIONS: Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.