IAS Gyan

Daily News Analysis

The participants we need in Phase 3 trials

28th August, 2020 Editorial

Context: While everyone else can avoid exposure to COVID-19, healthcare workers have to work in high-risk environments with repeated exposure to infection. Vulnerable groups such as the elderly and those with co-morbidities have five-fold to 15-fold greater mortality when they get COVID-19 than others. Therefore, healthcare workers and vulnerable groups need to be treated as priority categories for vaccination when the COVID-19 vaccine is available.

Protecting against COVID-19

  • Two COVID-19 vaccines have been accepted for Phase 3 trials after passing the Phase 1 trial for safety and the Phase 2 trial for both safety and the vaccine’s ability to induce a virus-neutralising antibody with or without T-cell-mediated immunity.
  • Vaccine-induced immunity has not yet been proven to protect against COVID-19, but the likelihood of protection is quite high for the following reasons.
  • Natural infection induces both a virus-neutralising antibody and T-cell-mediated immunity. Convincing reports of reinfection by the novel corona virus in previously infected individuals are extremely rare, suggesting that natural infection is indeed protective in the vast majority.
  • When a vaccine candidate produces similar immune responses, the probability of it being protective against the disease is high. A vaccine that has passed Phase 2 should therefore be assumed to be protective, unless proved otherwise in a Phase 3 trial, which will provide additional evidence of freedom from rare side effects.
  • Once cleared in Phase 3, the vaccine is registered by the drug regulatory agency and vaccination of the general public carried out as per national policy.


  • The objective of vaccination is three-fold: in the short term, to protect vulnerable individuals from serious disease and death; to protect occupationally exposed individuals from acquiring and unwittingly transmitting infection to their patients and family; and, eventually, to eradicate the viral infection.
  • The measure of effectiveness of a vaccine is how many infections and how many deaths it can prevent rather than how high the antibody titre will be, because antibodies are only surrogate markers of protection.
  • The drug regulatory agency should recognise this risk-based categorisation of the public and help design the Phase 3 trial in which vulnerable people and healthcare workers are preferentially given an opportunity to register themselves as volunteers.
  • Obtaining information on vaccine efficacy and safety from these subgroups is of paramount importance to facilitate prioritised vaccination of those who did not have an opportunity to enrol as volunteers for the trial and those who got placebo injection.

Why healthcare workers?

  • There are several reasons why healthcare workers, particularly those above age 55, should volunteer for and be included in Phase 3 trials. Historically, healthcare workers have often been the first to volunteer to participate in several physiological and pharmacological studies of an experimental nature. This attitude is more appropriate now than ever before in the context of COVID-19 vaccination trials.
  • Participation of healthcare workers will motivate members of the general public to participate in the trial and make recruitment easier.
  • Healthcare workers, in particular doctors and nurses, understand controlled clinical trials and the safety features in vaccine production and would be better able to provide informed consent.
  • Further, they will clearly understand that half the enrolled subjects receive only a placebo and therefore no one will flout personal protection norms even after receiving the vaccine trial injection.

Conditions apply

  • Conditions apply for inclusion of healthcare workers in the trial. Those healthcare workers who have already contracted COVID-19 and who do not need the vaccine will be listed in the National Registry.
  • Of those who have so far not been infected, IgG antibody testing will identify antibody positive subjects who do not need vaccination. Sero-prevalence of IgG antibody in healthcare workers is likely to be 30-40% as is the case currently in our metros; only the remaining proportion of healthcare workers will still be susceptible.
  • It should be possible to accommodate these eligible subjects into the Phase 3 trial protocol without much difficulty.

Reference: https://www.thehindu.com/opinion/lead/the-participants-we-need-in-phase-3-trials/article32459266.ece