Title: Clinical parameters in pre- and post-registration assessment of vaccine safety and efficacy.

POPLINE Document Number: 075897

Author(s):

Jones WR
Beale AJ

Source citation:

In: Vaccines for fertility regulation: the assessment of their safety and efficacy. Proceedings of a Symposium on Assessing the Safety and Efficacy of Vaccines to Regulate Fertility, convened by the WHO Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, June 1989, edited by G.L. Ada, P.D. Griffin. Cambridge, England, Cambridge University Press, 1991. :147-64. (Scientific Basis of Fertility Regulation)

Abstract:

The general scheme of development and clinical testing of a contraceptive vaccine, then specific tests to be performed for clinical monitoring of Phases 1,2,3, and postregistration assessment of vaccine users are outlined. The objectives of phased clinical trials are: Phase 1) pharmacology of the drug in healthy volunteers; Phase 2) dose-finding and pharmacology of the agent in patients; and Phase 3) extended clinical trials in patients for clinical efficacy, acceptability, and assessment of side effects. Phase 1 trials of a contraceptive vaccine have unique ethical and legal aspects, since reversibility of the vaccine cannot be assured, and absence of a teratological effect cannot be guaranteed. Special steps must be taken for legal indemnity of all agencies involved, and national drug regulatory agencies have to learn new strategies for this kind of drug. Australia has found recruitment of subjects for Phase 1 trial very difficult. Criteria for selection of subjects for phase 1,2, and 3 trials are listed. The protocol and clinical investigations done during the trials are also tabulated. Subject monitoring included physical exam and nonspecific studies of biochemical and hematologic parameters, and specific immunological and endocrine tests for immune complexes, autoimmunity, muscle damage, hypersensitivity, and cross reaction to several peptide trophic hormones. Parameters added for Phase 2 trials include assessment of efficacy: serial serum assays for antibodies to hCG, serum progesterone assays and serum pregnancy tests. For Phase 3 trials, it is estimated that 1000 subjects for at least 10,000 months in a randomized comparative trial will be sufficient to demonstrate safety and efficacy. HLA typing was also advised for Phases 1, 2, and 3, to study genetic variations in specific responses. Acceptability will be in question if more than 1 administration is needed, if testing for efficacy is needed, the time between boosters is severely limited, or if special procedures are needed to monitor autoimmunity or vaccine response.

Keywords:

Clinical Trials
Recommendations
Biological Characteristics
Vaccines
Contraception Research
Contraception, Immunological
Laboratory Examinations and Diagnoses
Human Volunteers
Informed Consent
Ethics
Side Effects
Clinical Research
Research Methodology
Biology
Contraception
Family Planning
Examinations and Diagnoses
Treatment