Clinical evaluation of vaccines

Clinical evaluation is a critical step to support the approval of vaccines. Given the limitations of animal models, clinical studies to demonstrate the safety and efficacy of vaccines must be conducted in humans before a vaccine can be released for widespread use. The design and conduct of these clinical studies will remain a challenge to manufacturers and regulatory authorities alike. For example, if the aim of the clinical study is to evaluate the ability of the vaccine to provide protection against infection, often large numbers of patients must be enrolled in the study to generate sufficient data to be statistically meaningful. When protection against disease is not a suitable outcome of the clinical study, measurement of immune responses to the vaccine could be an alternative approach. However, this must be defined based on scientific assumptions and require confirmation of clinical efficacy after its approval (post-marketing evaluation). There is also a pronounced ethical aspect of running clinical trials on healthy patients, and in particular in infants.

Clinical evaluation of vaccines guidance

Written Standards

The WHO guidelines on clinical evaluation of vaccines were approved by the Expert Committee for Biological Standardization (ECBS) in 2001. They were developed in response to requests from national regulatory authorities for assistance in the evaluation of clinical trials, both during the clinical development of a new vaccine and also during the regulatory review of dossiers submitted in support of applications for marketing authorizations (approval for use).The guidance document also outlines the data that should be obtained during the different stages of vaccine development in order to support a marketing approval and establishes international guidance to govern the protection of individual patient while safeguarding public health. In 2016 the guidelines were updated to reflect the scientific and regulatory experience that had been gained from vaccine clinical development programmes since the adoption of the 2001 version:

Guidelines on clinical evaluation of vaccines: regulatory expectations; TRS 1004, Annex 9. Replacement of Annex 1 of WHO Technical Report Series, No. 924

In the drafting of the Guidelines on clinical evaluation of vaccines it became evident that one subject which had not been covered was regarding human challenge trials (also known as controlled human infection studies). However, as human challenge trials are not a requirement for licensing it was felt that guidance should be provided within a separate document and to be considered within conjunction with the above Guidelines on the clinical evaluation of vaccines:

Human challenge trials for vaccine development: regulatory considerations, TRS 1004, Annex 10

In addition to the guideline developed by WHO, guidelines on various aspects of clinical trials of vaccines are available from regulatory bodies such as the :

Issues specific to the clinical evaluation of individual vaccines are now being addressed in a separate section in revisions of the guidance document for each vaccine.