Strict monitoring and surveillance systems for the safety of all vaccines, including for Covid-19, are in place during trials and when shots are rolled out more widely.

(Photo: / Wikipedia)
The South African Health Products Regulatory Authoritys (Sahpras) recommendation at the weekend to lift the temporary suspension of the use of the Johnson & Johnson (J&J) Covid-19 vaccine in the Sisonke phase IIIB implementation study, has rekindled hopes that the phased roll-out of the vaccine will press ahead and more doses will soon get into more peoples arms.
The pause of the J&J vaccine on 13 April gave rise to concerns about its safety and fears that the move would increase vaccine hesitancy. Sahpras decision was in line with the US Food and Drug Administrations decision to do the same in that country following reports of rare adverse events. No similar adverse events have been reported in South Africa.
The imminent lifting of the suspension in South Africa means the Sisonke study should start vaccinating people again within a few days. The study, part of Stage One of the national roll-out, aims to vaccinate half a million frontline healthcare workers. About 300,000 have been vaccinated so far.
Registration for Stage Two of the roll-out is under way.
On 17 May, vaccination is scheduled to begin for five million citizens 60 and older, 12 million essential workers and those with comorbidities.
Spotlight asked Hannelie Meyer, professor in the School of Pharmacy and head of the South African Vaccination and Immunisation Centre at Sefako Makgatho University, and Florah Matlala from Sahpras Pharmacovigilance Unit to explain how vaccines are monitored for safety after they are rolled out to the public.
The South African Health Products Regulatory Authority authorises, monitors and evaluates all clinical trials in South Africa. (Photo: / Wikipedia)
How does safety monitoring work? 
Sahpra and the Department of Healths Expanded Programme on Immunisation is central to South Africas monitoring and surveillance system. Reporting of adverse events following immunisation has always been part of the programmes monitoring and evaluation process. In 2017, the adverse events surveillance system was strengthened, with reporting and investigation responsibilities at district, provincial and national levels as well as in the private sector.
Sahpra authorises, monitors and evaluates all clinical trials in South Africa.
Meyer says there is strict safety monitoring (pharmacovigilance) during all three phases of clinical trials, but no clinical trial can be powered to detect rare or very rare adverse events. It is only when a vaccine is rolled out to large populations that rare adverse events can be picked up. 
Safety monitoring continues when Sahpra registers a vaccine for use in the general population. This post-marketing surveillance determines the long-term risks and benefits of the vaccine, and identifies if there are any rare or very rare adverse events following immunisation or adverse events that are slow to manifest. Matlala says Sahpras mandate includes ensuring that a pharmacovigilance system for health products is in place.
Safety monitoring continues when Sahpra registers a vaccine for use in the general population. (Photo: / Wikipedia)
What is a rare or very rare adverse event?  
Rare adverse events occur between one in 1,000 and one in 10,000 doses, while very rare events occur in fewer than one in 10,000 doses.
For these events, one needs to weigh the risks and benefits of vaccination, says Meyer.
Using the recent case of the rare blood-clotting condition identified in six out of 6.8 million people who received the J&J vaccine in the US as an example, Meyer says the risk of thrombosis (clotting) following vaccination is fewer than one in a million people or 0.000088%, while the risk in severe Covid-19 cases is between 20% and 30%.
There are other compounding risk factors that might have been present, which is why the Food and Drug Administration is conducting an in-depth investigation of these cases, says Meyer.
We know that, for example, smoking, injury, immobility, genetic factors and other medicines such as oral contraceptives predispose people to the risk of thrombosis. Furthermore, Covid-19 infection itself is associated with blood clots and one of the major causes of death, hence a much higher risk factor to consider. 
Meyer says that even if this rare condition is associated with the vaccine, the risks of developing thrombosis from Covid-19 infection or dying from the disease are much higher. The AstraZeneca vaccine, which is not used in South Africa, uses a similar approach to the J&J shot and although the Food and Drug Administration and the European Medicines Agency reported a plausible link between the AstraZeneca jab and thrombosis, this is also extremely rare. 
A South African health worker receives the Johnson & Johnson Covid-19 vaccine. (Photo: EPA-EFE / NIC BOTHMA)
Who is responsible for adverse event reporting and monitoring?
Meyer says all healthcare workers who provide immunisation services, those providing clinical treatment of adverse events in health facilities and clinical trial researchers are responsible for reporting these events. Vaccine recipients are also encouraged to report them. 
In addition, Matlala says that according to the Medicines and Related Substances Act 101 of 1965, as amended, pharmaceutical companies must monitor the performance of their medicines and vaccines on the market and report any adverse effects to the regulator. 
Adverse event reporting and notification in South Africa takes place through passive surveillance or spontaneous reporting. Meyer says the system is useful for identifying potential safety signals or concerns for adverse events that were unknown at the time of a vaccine roll-out or are unexpected. However, it does not collect data from all vaccine recipients, as in a clinical trial, and it is unable to differentiate between a genuine reaction following immunisation and a coincidental event.
The Expanded Programme on Immunisation uses a paper-based system for reporting adverse events.
In addition to the electronic vaccination data system developed for Covid-19 vaccine registration and recording of vaccination, an electronic system for the reporting of adverse events is now available, Meyer says.
The Med Safety App (Android and iOS) allows the reporting of suspected adverse drug reactions for medicines and adverse events for vaccines. Matlala says the public can use it to report adverse drug reactions, but only health workers can use it to report adverse events following immunisation.
All adverse events following immunisation reported through the surveillance system are shared with Sahpra, which uploads them to a global pharmacovigilance database VigiBase® which is maintained by the Uppsala Monitoring Centre under the umbrella of the World Health Organization International Drug Monitoring Programme, a collaboration of more than 150 countries.
What is a safety signal? 
A safety signal is when adverse events following immunisation reports suggest a potential causal association between a vaccine and an event, and when it is considered important enough to justify investigation or verification. Meyer says the blood-clotting condition linked to the J&J vaccine is a signal of an unusual situation requiring investigation.
Meyer says pooling data from different countries once a vaccine has been rolled out to a large population is best for signal detection. Future electronic reporting of adverse events following immunisation in South Africa through the Med Safety App will allow this, since data will be pooled with Nigeria, Ghana and Ethiopia. Signals will be reviewed by a committee of experts from the four countries, with support from the regulatory authority in the UK.
She says detecting and investigating any safety signal is an extremely important aspect of the safety monitoring of new vaccines, because it means precautionary measures can be taken such as using a vaccine in certain populations and not in others and ensuring necessary management protocols are in place should a rare event occur.
What happens when a serious or severe adverse event is reported?
When any adverse event is reported a multidisciplinary healthcare team begins an investigation. All events must be reported within 24 hours of identification or when a vaccinated person informs their healthcare provider. All reported events are monitored very closely, says Meyer. 
Symptoms are treated and a case investigation is then set up. All information and reports are collated for serious events and clusters and are usually completed within 48 hours of reporting.
The National Immunisation Safety Expert Committee then reviews all the information and assesses whether there is a real safety concern with the vaccine, whether the event was coincidental or due to an underlying health issue. The Covid-19 Ministerial Advisory Committee on Vaccines also weighs in on assessments.
Matlala says that depending on the outcome of an investigation into a serious adverse event, the regulator may request changes to the product information, including the package insert and the patient information leaflet. These changes will stipulate specific contraindications for use, special precautionary measures to take or special warnings with the use of such a product.
In the case of the J&J implementation study, Sahpra recommended that the pause be lifted provided certain conditions are met, including changes to the screening process to include, specifically, participants who are at risk of any blood-clotting disorder, changes to the information provided to participants and the consent forms.
There should also be measures in place to ensure monitoring of participants who are at high risk of a blood-clotting disorder and the management of participants who do develop vaccine-induced thrombosis and thrombocytopenia, says Matlala. 
All healthcare workers who administer vaccines, including the Covid-19 jab, are trained in how to handle and administer the vaccine and manage and report adverse events. Every Covid-19 shot administered is recorded on a national register and all vaccinated people are given a vaccination card. Systems are being implemented to allow any person who has received a Covid-19 vaccine to personally report adverse events, including on the app. 
What is the potential for an increase in vaccine hesitancy?
The pause in the J&J vaccine roll-out demonstrates that vaccine safety monitoring works extremely well, and in a perfect world that would build public confidence in vaccination, says Meyer. However, we dont live in a perfect world, so the pause can potentially be harmful to vaccine confidence in general and subsequently vaccine hesitancy will rise. 
She says the focus on the rare adverse event following J&J vaccination was negatively affecting peoples perceptions. However, the event is extremely rare and people forget that the risks of severe outcomes from Covid-19 infection are much higher.
Misinformation spreads very rapidly, especially on social media, which then fuels vaccine hesitancy and vaccine refusal among those people who do not verify information and indiscriminately share information within their own networks. This has the potential of having a devastating impact on public health. DM
Adele Baleta is an independent science writer and a member of the Vaccine Hesitancy Working Group for the National Advisory Group on Immunisation.
This article was produced by Spotlight health journalism in the public interest.
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