A THREAD on the detection of associations between Covid-19 vaccines and adverse events. Detection of adverse events currently relies on four main approaches: clinical trials, prescription event monitoring, spontaneous reporting and analysis of large clinical databases. 1/

Clinical trials may fail to detect rare adverse events. Prescription event monitoring aims to detect an excess risk of adverse events in users of newly-marketed vaccines, but is limited by relatively short follow-up time and by the difficulty of selecting appropriate controls. 2/

Spontaneous reporting relies on clinicians and patients recognising adverse reactions and their readiness to report them to national pharmaco-vigilance authorities. Even for serious and well-recognized adverse reactions, spontaneous reporting rates are often low. 3/

In recent years, the use of data from large clinical databases derived from medical records has become increasingly common for the detection of adverse reactions to vaccines, often using case-control designs. The use of case-crossover studies has also become common. 4/

Case-crossover designs are based on events among individuals after receiving a vaccine and events in the same individuals before they received a vaccine. Because each individual is included both as a case and a control, the case-crossover design can reduce confounding. 5/

Because adverse events can be very rare, large numbers of people receiving vaccines are required to identify a potential association of an adverse event with a vaccine. For some adverse reactions, international studies may be needed to further increase the sample size. 6/

Patients with very rare medical conditions now asking their clinicians what the risk-benefit ratio is for them following vaccination. It will take time to generate this data but in general, for people with long-term conditions, vaccination protects against serious illness. 7/

Finally, the benefits of Covid-19 vaccination for individual patients and for populations far outweigh the very small risk of the serious side effects that have been identified in the routine use of these vaccines. It’s important to remind people of this fact. 8/