Several issues raised by the authors are beyond the scope of discussion as
my original article did not cover those topics. Following are some of my
thoughts relevant to remarks by Drs Kalra and Vashishtha.
To me the first and foremost important authority is the
local regulatory authority in any country as far as a ‘stamp’ of
authenticity is concerned. However other bodies like ICMR/IAP etc
recommending use of any vaccine will make it more acceptable for the
practitioners. There is a mention of demerits of the conjugate Vi vaccine
marketed in India in the IAP Immunization Guidebook 2008(1).
Typically any new vaccine (or for that matter any new
drug) has to undergo phase 1 (early safety and dosing study), phase 2
(safety, dosing and immunogenicity study) and phase 3 (field efficacy and
further safety study) trials before being licensed(2). In case one brand
of the concerned vaccine with satisfactory efficacy data is already
licensed, and serological correlates of protection for the vaccine are
clearly known, a new brand need not do efficacy trials and can be licensed
provided it shows non-inferiority (not more than 10% lower than for the
lower CI) in comparative immunogenicity trials. Such non-inferiority
results will assume and extrapolate similar efficacy for the new brand as
compared to the existing vaccine (what is called bridging studies)(3). The
new brand has to show non-inferiority over the existing brand in
seroconversion (not more than 10% lower for the lower confidence interval
compared to the existing brand) and GMCs (not less than 0.5 times as
compared to the existing brand).
However if the serological correlates of protection are
not known for a vaccine, one has no choice but to conduct field efficacy
trials to prove non-inferiority compared with the existing licensed
vaccine, example of such vaccines being pertussis vaccines for which huge
and expensive field efficacy trials were conducted by most
manufacturers(4); and typhoid vaccines. Serological correlates of
protection are not known for the existing unconjugated Vi vaccine, oral
Ty21a vaccine or the old whole cell killed typhoid vaccines. This is the
reason why for each of these vaccines field efficacy trials have been
conducted and reported(5). This is the reason why other Indian
manufacturers are busy conducting field efficacy trails with their own
candidate conjugate Vi vaccine(2).
References
1. Singhal T, Amdekar Y, Agarwal R. IAP Guidebook on
Immunization: IAP Committee on Immunization 2007-2008. New Delhi: Jaypee;
2009; p. 57.
2. Clemens J. Translational research to generate
evidence for rational and efficient introduction of new vaccines in
developing countries: The experience of the International Vaccine
Institute. Ann Nestle 2008; 66: 81-91.
3. Jódar L, Butler J, Carlone G, Dagan R, Goldblatt D,
Käyhty H, et al. Serological criteria for evaluation and licensure
of new pneumococcal conjugate vaccine formulations for use in infants.
Vaccine 2003; 21: 3265-3272.
4. Cherry JD. Comparative efficacy of acellular
pertussis vaccines: an analysis of recent trials. Pediatr Infect Dis J
1997;16: S90-96.
5. Engels EA, Matthew EF, Joseph L, Michael LB. Typhoid
fever vaccines: a meta- analysis of studies on efficacy and toxicity.
British J Med 1998; 316: 110-116.