Vaccine Safety vs. Hesitancy: Cause, Common Themes & Interventions

As the world draws closer to receiving vaccines that are officially approved by the US Food & Drugs Administration (FDA), more than a few dozen countries have taken proactive steps and have begun vaccinating their population.

This couldn't have come at a better time: at the start of February 2020, the number of active cases has soared to more than 25.9 million, with a total of 2.2 million deaths.

While most countries are eagerly awaiting their supply of vaccines, another pressing issue remains: vaccine hesitancy. 

Establishing Vaccine Safety & Effectiveness Through Clinical Trials

Vaccines (like any other drug) undergo a rather lengthy and exhaustive process even before they are approved for public use. In a nutshell, every vaccine needs to be tried and evaluated in various stages:

1. Pre-Clinical Stage – When a ‘target’ of a virus is identified for example, thousands of compounds are researched in labs, before they are tested on animals.
2. Phase 1 Clinical Trial – The few compounds (candidates) that are deemed safe for human trials are tested on healthy volunteers first (to determine their safety).
3. Phase 2 Clinical Trial – This phase involves more volunteers to determine their effectiveness (whether the drugs work on a larger sample or not).
4. Phase 3 Clinical Trial – A large scale trial (involving thousands of volunteers) to determine more about a vaccine’s safety & effectiveness, while determining the best dosage possible dosage.
5. Review & Approval Stage – Once a vaccine completes all of the above, the FDA will review the findings (large amounts of documented data, side effects, etc.) before giving the approval.
6. Post-Marketing Stage – Even after a vaccine is approved, the pharma companies are required to provide periodic safety updates. There is also a system in place that allows the public (including healthcare providers) to report adverse side effects or other concerns.

At any point if a vaccine candidate fails to demonstrate the required safety and efficacy, it would be scrapped. If there are no candidates left, the pharma company would have to go back to the drawing board.

Needless to say, no vaccine would be approved for public use if it was deemed unsafe or ineffective. To know more about clinical trials and the drug approval process, click here.

Vaccine Side-Effects Are Well Documented

Vaccines, like any drug, have side-effects. And as with all drugs, no vaccine manufacturer is hiding those side effects. Authorities such as FDA and CDC have taken steps to ensure transparency by listing all known side-effects and dosage guidelines of vaccines.

Most of the reported side-effects are minor. Adverse side-effects are documented thoroughly and are considered so rare that it’s considered impossible to link them conclusively to the vaccines.

As vaccines are vetted by the FDA for public use, their ingredients are listed in detail and are also available online. 

Vaccine Effectiveness

Scientific evidence for the effectiveness of large-scale vaccination campaigns is well established. 2-3 million deaths are prevented each year worldwide due to vaccination.

An additional 1.5 million deaths could be prevented each year if all recommended vaccines were used. Vaccination campaigns helped eradicate smallpox, which once killed as many as one in seven children in Europe, and has nearly eradicated polio.

As a more modest example, infections caused by Haemophilus influenza (Hib), a major cause of bacterial meningitis and other serious diseases in children, have decreased by over 99% in the US since the introduction of a vaccine in 1988.

It is estimated that full vaccination, from birth to adolescence, of all US children born in a given year, would save 33,000 lives and prevent 14 million infections. 

Addressing Vaccine Hesitancy

Vaccine hesitancy, also known as anti-vaccination or anti-vax, is a reluctance or refusal to be vaccinated or to have one's children vaccinated against contagious diseases. The term encompasses:

1. Outright refusal to vaccinate
2. Delaying vaccines
3. Accepting vaccines but remaining uncertain about their use
4. Using certain vaccines but not others

Vaccine hesitancy is responsible for decreasing vaccine coverage and an increased risk of vaccine-preventable disease outbreaks and epidemics. It is identified by the World Health Organization as one of the top ten global health threats of 2019.

Cause of Vaccine Hesitancy

Hesitancy primarily results from public debates around the medical, ethical and legal issues related to vaccines. In a nutshell, vaccine hesitancy stems from multiple key factors:

1. A person's lack of confidence (mistrust of the vaccine and/or healthcare provider).
2. Complacency (the person does not see a need for the vaccine or does not see the value of the vaccine); and
3. Convenience (in certain places, access to vaccines are limited).

Common Themes of Hesitancy

Various themes about vaccination have been raised over recent decades. These themes have been addressed and are usually not supported by scientific evidence.

Some of the more popular themes include:

1.    Autism – Originated from a fraudulent 1998 study (published in The Lancet) by British doctor Andrew Wakefield. The study was retracted when The Sunday Times (in 2009) exposed Andrew of manipulating the patient. The British Medical Journal also described how Andrew falsified data (in 2011) so that he would arrive at a predetermined conclusion. Andrew was stripped of his license to practice medicine. Cases of autism are perceived to be on the rise due to better understanding, identification & diagnosis of autistic children.

2.    Safety – Thimerosal (an antifungal preservative used in small amounts in some multi-dose vaccines) contained mercury. In 1999, CDC and AAP (American Academy of Pediatrics) ordered the removal of the preservative due to safety concerns. Despite this, cases of autism (a side-effect initially thought to be associated with thimerosal) continued to increase steadily.

3.    Vaccine Overload – A non-medical term that if a child was given 'too many' vaccines at once, it would overwhelm or weaken the child’s immune system. Despite the increase in the number of vaccines over recent decades, improvements in vaccine design have reduced the immunologic load from vaccines; the total number of immunological components in the 14 vaccines administered to US children in 2009 is less than 10% of what it was in the 7 vaccines given in 1980.

Other themes include:

1. Ingredient concerns
2. Sudden infant death syndrome
3. Anthrax vaccines
4. Vaccine myths, including natural infection, etc.
5. Conspiracies on capitalism, government surveillance, etc.

How does an anti-vax develop? In most cases, concerns about vaccine safety often follow a pattern. It starts with some investigators (who usually lack certain qualifications) suggest that a medical condition of increasing prevalence or unknown cause is an adverse effect of a vaccine.

The initial study and subsequent studies by the same group have inadequate methodology — typically a poorly controlled or uncontrolled case sample or series. This leads to a bias that skews results in their favour.

A premature announcement is made about the alleged adverse effect, resonating with individuals suffering from the condition, and underestimating the potential harm of forgoing vaccination to those whom the vaccine could protect.

Other groups would then attempt to replicate the initial study but fail to get the same results. Finally, it takes several years to regain public confidence in the vaccine.

A recent misconception that if vaccines are a ‘weakened’ or ‘altered’ form of pathogens (virus & bacteria), there is a risk of exposure towards the disease. This is mostly due to a lack of understanding (knowledge deficit) on the overall concept of vaccines.

Interventions that Focus on Spreading Awareness

Vaccine-hesitant parents who are on the fence far outnumber vaccine refusers; therefore, targeting this group for vaccination is more effective.

Local governments should organize awareness campaigns to increase knowledge and awareness surrounding vaccination.

Reasons behind vaccine hesitancy are complex and encompass more than just a knowledge deficit. Local governments, however, can start by targeting specific populations (local communities & healthcare workers). As a trusted source of information on vaccines, family physicians and healthcare workers play a key role in driving vaccine acceptance.

Interventions that Employ Thought Leaders & Influencers

Local health departments can work with influential leaders to promote vaccination in their communities. Influencers, be it those who are famous on social media and religious leaders can play a pivotal role in getting the message across.

With enough awareness campaigns running concurrently and consistently, it would encourage a form of 'psychological shift' that would change attitudes in those who are hesitant towards vaccines to become pro-vaccines in the long run.

WHO SAGE suggests that the above intervention strategies (when used in combinations), was found to be most successful in increasing the overall vaccine uptake of local populations.

Sources:

1.    WHO International

2.    "Strategies For Addressing Vaccine Hesitancy – A Systematic Review" by WHO SAGE working group

3.    https://time.com/5530611/vaccines-safe-effective/

4.    https://content.time.com/time/subscriber/article/0,33009,1808620,00.html

5.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515949/

6.    https://pubmed.ncbi.nlm.nih.gov/32242766/

7.    https://pubmed.ncbi.nlm.nih.gov/23584253/

8.    https://pubmed.ncbi.nlm.nih.gov/11293594/

9.    https://pubmed.ncbi.nlm.nih.gov/11925021/

10. https://en.wikipedia.org/wiki/Vaccine_hesitancy