Vaccines are a matter of pride for every nation and undoubtedly a life-saving biological innovation. The invention of vaccines dates back to the 17th century, and they have helped in building immunity against several contagious and life-threatening diseases known to humans. We all have been administered with various vaccines, generally in our early years. Vaccines like BCG, polio, diphtheria, hepatitis, measles, chickenpox, rotavirus & HPV vaccines have helped in preventing and even eradicating diseases.
While we take comprehensive measures to keep the Coronavirus at bay, we also await the release of the much anticipated COVID-19 vaccines. The good news is that a few of them have already reached the phase 3 stage of clinical trials. Let us take a closer and deeper look at what is done in clinical trials, and how their outcomes dictate the subsequent steps.
What happens in a clinical trial?
A clinical trial is conducted to primarily test new biological innovations such as medicines and vaccines. Ideally, a group of healthy people are carefully selected for participation and are subjected to the active ingredient of the vaccines to test its efficacy and potential side effects.
To evaluate the real potential of the vaccine, a control, often called the ‘placebo treatment’ also runs in parallel. Certain participants are given a placebo instead of the actual vaccine, to check if the progress and reactions are due to the active agent given in a standard dose or whether it is caused by psychological factors.
Further, the trials are conducted in three phases with volunteers of specific age groups, ethnicity and sex, to do a deep analysis of the pros and cons of the vaccine.
The 3 phases of clinical trials:
Phase 1 Trial
- In phase 1, for the first time, the vaccine is introduced and administered to a small group of selected volunteers.
- Gradually, the vaccine dosage is altered and increased among the same group following standard protocols.
- Researchers minutely observe all minor and major side-effects and the positive effects of the new vaccine.
Phase 2 Trial
- In this phase, the researchers replicate the same procedure followed during the first trial on a slightly larger population, generally in the 100s.
- During phase 2, the selection of volunteers is also made eclectic, that is a mixture of healthy candidates and people suffering from illnesses or other co-morbid conditions.
- The mixed volunteers are then subjected to the vaccine and this is done to better understand the reactions and effectiveness of the vaccine.
Phase 3 Trial
- Phase 3 is considered the most important phase as the vaccine has now passed two trials and has been thoroughly studied.
- The trials in phase 3 are done on a very large population which includes thousands of people. The trials at this stage can go up to 12 months or more.
- The placebo effect is also brought into play to know about post-vaccination immunity over the natural immunity of the volunteers.
- If at any stage during this phase, any unusual or severe reactions are observed even in a small group, or a single member, the vaccine development is paused until it is considered safe and given the go-ahead by the safety scientific community.
Regulatory review and approval
- After clinical trials of phases 1, 2 and 3, the results are reviewed and the data carefully analyzed to understand the safety, efficacy and readiness of the candidate vaccine.
- Major approvals, licensing, marketing and administering rights are given during this stage, before making it commercially available for public health use.
In the past, vaccines have taken a lot of time to come to the market due to strict scrutiny and safety measures during the trials. However, in the case of COVID-19 vaccines, the entire process has been accelerated and is progressing at a blistering pace, given the nature of the pandemic.
It is worth noting that several vaccines journeys hit bumps that are related to side effects that some participants experience. There are protocols to be followed at such events which are closely monitored by regulatory bodies.
Common side-effects of vaccines
The vast majority of people will not experience any serious side effects from vaccines. However, there are the usual and common side effects like tenderness at the place where the shot was given. There are also a few other side effects known to be caused by vaccines.
- Joint and muscle pains
- Allergic site reactions (redness & soreness)
Usually, these reactions are mild or moderate in nature and will go away within 1-2 days without much medical intervention.
COVID-19 vaccines and reported side effects during trials
In all the COVID-19 clinical trials, a few participants experienced mild and moderate effects, such as fatigue, chills, headache and muscle pain after being vaccinated. These participants have gone on to quickly recover from their condition. However, a couple of them, notably Oxford/AstraZeneca and J&J (Janssen) candidate vaccines have reported one incident each of a Serious Adverse Effect (SAE) in Phase 3. Under such circumstances, both the clinical trials were paused for a safety review and the trial’s enrolment was also put on hold.
In the case of Oxford-AstraZeneca, a participant in the UK had developed a serious reaction in early September. While AstraZeneca disclosed limited information about the nature of the illness, it was later revealed that the patient had reportedly developed a neurological disorder. After safety review by various regulatory bodies, the trials have resumed in the UK, India and other parts of the world. However, the trial is still paused in the US by the FDA.
J&J also paused it’s Phase 3 clinical trial in mid-October after a participant developed an unexplained illness after taking the COVID-19 vaccine. The company is still reviewing what led to the illness, and are also presently understanding if the sick participant was a person who got the vaccine or the placebo; and whether it was actually a vaccine-related reaction or the candidate suffered from a pre-existing condition.
While these events seem to be brief setbacks in the development of the vaccine, it reinforces the need for all prospective vaccines to go through the complete rigour of all the necessary processes and clinical trials, to deliver a successful COVID-19 vaccine. Both companies have pledged that they will not release a vaccine until safety data is sufficient.
Scientists are still trying to develop reaction-free vaccines to combat, eradicate and protect us against the different Coronaviruses. This discovery will not be easy as we may require different vaccine doses and types depending upon ethnicity, other factors such as age, co-morbid conditions, pregnancy and adaptive immune response varying from person to person. Nevertheless, vaccines have been successfully developed in the past to conquer even more dangerous diseases, and we shall do so this time as well.
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