Communicating for the Safe Use of Medicines: Progress and Directions for the 2020s Promoted by the Special Interest Group of the International Society of Pharmacovigilance: An International Journal of Medical Toxicology and Drug Experience

Bahri et al discuss the International Society of Pharmacovigilance's (ISoP) Special Interest Group on Medicinal Product Risk Communication (CommSIG). ISoP dedicated a range of activities to communication about the risks and safe use of medicines in the decade before creating the CommSIG, including a pre-conference training course in Tianjin in 2014. Establishing the CommSIG also built on a forward-looking attitude to changes in medicine, communication technology, patient expectations, and societies overall. It was also recognized that the multidisciplinary approach to communication would support reaching out to patient groups, healthcare, medicine information and media professionals, and experts from the communication, social, healthcare and data sciences. The nine founding members of the CommSIG published its background and aspirations in ISoP's official journal, Drug Safety.

When I use a word . . . . Taking therapeutic care.

In healthcare there are different forms of taking care or taking precautions. When using a therapeutic intervention, one takes care by implementing it appropriately. When the appropriate intervention is pharmacological that means giving an appropriate formulation of a medication in an appropriate dosage regimen. If the intervention might cause harm, but the benefit:harm balance is favourable, one might do nothing apart from monitoring or one might introduce a preventive strategy, such as the use of mesna when giving an oxazaphosphorine such as cyclophosphamide. Vaccination and contraception are both examples of precautionary measures that have an excellent benefit:harm balance. But when the benefit:harm balance of an intervention is unfavourable the precaution to be taken is avoidance of the intervention. That, and only that, form of precaution, avoidance to avoid harm, is a defining feature of the precautionary principle.

Spontaneous Reporting to Regulatory Authorities of Suspected Adverse Drug Reactions to COVID-19 Vaccines Over Time: The Effect of Publicity.

INTRODUCTION: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area. OBJECTIVE: Our objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates. METHODS: We used publicly available data on reports of suspected ADRs and doses of vaccine administered, published by the MHRA, EudraVigilance, and the European Centre for Disease Prevention and Control to calculate reporting rates. RESULTS: Approximately 4814 Yellow Card reports (23 fatal) per million doses of ChAdOx1 nCoV-19 (AstraZeneca) and 2890 (13 fatal) per million doses of tozinameran (Pfizer/BioNTech) have been lodged. Between 15 March and 31 October 2021, cumulative European reports of CVST rose from 0 to 443 (183 with thrombocytopenia, 72 fatal) with ChAdOx1 nCoV-19 and from 2 to 315 (9 with thrombocytopenia, 28 fatal) with tozinameran. European cases of retinal vein occlusion and thrombosis rose from 0 to 168 with ChAdOx1 nCoV-19 and from 1 to 220 with tozinameran; four of the ChAdOx1 nCoV-19 cases were associated with thrombocytopenia. CONCLUSION: Reports of fatal adverse reactions to coronavirus vaccines are very rare. Reports of CVST have been made in relation to both vaccines. Most were submitted after the reaction had been publicized. Thrombocytopenia occurred in a minority of cases. Reports linked both vaccines to cases of retinal vein thrombosis, just four cases with thrombocytopenia. This suggests two different mechanisms of thrombosis associated with the vaccines.

When I use a word . . . . No jab, no job? A benefit:harm balance analysis.

The current debate about whether individuals should be entitled to work in the healthcare sector if they decline to be vaccinated against SARS-CoV2 has been largely informed by personal opinions and argument by analogy. A benefit:harm balance analysis suggests that while vaccination has a highly favourable benefit:harm balance, the balance in instituting a "no jab, no job" policy is highly uncertain and may be unfavourable. Furthermore, there are practical difficulties and legal uncertainties. The much misunderstood precautionary principle dictates that if the benefit:harm balance of an intervention is unclear and may be unfavourable, the intervention should not be undertaken. Furthermore, the onus is on those who believe that the benefit:harm balance will be favourable to prove that it is so; it is not for the sceptics to prove that it isn't. In the absence of good evidence in favour, this is an intervention that would be best avoided.

When I use a word . . . . Examining the efficiency paradox.

Healthcare involves tackling patients' problems using many different types of resources, both human and technological, and the spaces in which they operate. Variability in, on the one hand, human abilities, the performance of technologies, and the available facilities, and, on the other, the problems that patients present with distorts our ability to maximize the efficiency with which we use healthcare resources while minimizing the time a patient spends in the healthcare system and the inconvenience involved. Variability in demand and lack of resources also contribute. The efficiency paradox is that in healthcare efficient use of resources tends to increase the time a patient spends in the system and the inconvenience involved. But the efficiency paradox is not a paradox at all. It is a consequence of identifiable problems in the way that healthcare is delivered, albeit without identifiable solutions that can be simply implemented.

The use of mechanistic reasoning in assessing coronavirus interventions.

RATIONALE: Evidence-based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies. AIMS AND OBJECTIVES: To explore examples of the importance of mechanistic evidence to coronavirus research. METHODS: We have reviewed the mechanistic evidence in four major areas that are relevant to the management of COVID-19. RESULTS AND CONCLUSIONS: (a) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (b) That hypertension is a risk factor for severe disease in the case of SARS-CoV-2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (c) Confidence that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (d) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework.