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Biomedical subjects

A D Horne

Publications and source records attributed to A D Horne.

14 recordsLinked to original sources
PubMed2001

Analysis of studies to evaluate immune response to combination vaccines.

The development and evaluation of new combination vaccines is an important public health endeavor. Trials to evaluate these vaccines are customarily designed and analyzed as noninferiority studies. We explain the concept of noninferiority and highlight important issues that can be challenging in the statistical evaluation of these vaccines. Topics covered include end points, hypotheses, and analyses for comparing geometric mean concentrations (or titers) of antibody and proportion of vaccine recipients responding; covariate adjustment; the problem of multiplicity and its impact on sample size; and choice of a meaningful difference to rule out.

Antibodies, Bacterial↗
PubMed2001

Evaluating the immune response to combination vaccines.

Assessment of the immune responses to combination vaccines in the United States has generally been based on randomized, controlled comparative trials, with such studies designed to rule out predefined differences. In designing clinical studies of the immune response to combination products, attention should be directed toward selecting the appropriate immunologic end points and control groups. Acceptable differences in immune responses between combination and control groups should be predefined, and an adequate statistical plan should be developed. In many cases, it may be necessary to evaluate simultaneous administration of other recommended vaccines, assess schedule changes for 1 or more components of a combination, and bridge immunologic data obtained from international studies to the population of the United States. We discuss the use of immunogenicity studies to support the licensure of combination vaccines when field efficacy studies are either not possible or not required and highlight some recent experiences with combination vaccines containing Haemophilus influenzae type b polysaccharide conjugates.

Antibodies, Bacterial↗
PubMed2000

Intent-to-treat analysis and preventive vaccine efficacy.

While the intent-to-treat (ITT) concept has often been discussed and debated in the literature with respect to randomized, placebo-controlled therapeutic trials, there has been little discussion of this issue in the context of preventive vaccine efficacy trials. ITT analysis has traditionally played a minor role (if any) in the latter trials. This paper discusses the ITT approach to analysis in randomized superiority trials of preventive vaccine efficacy, using clinical endpoints. Data are presented from published literature as well as from a simple mathematical model. The data suggest that when compliance and efficacy are high, both ITT and "per-protocol" approaches generally lead to similar conclusions regarding the acceptability of a vaccine for use in a population. However, when compliance is low, the ITT and per-protocol estimates of vaccine efficacy can be widely disparate. ITT and per-protocol analyses address unique and relevant scientific questions, and often both will be informative in evaluating preventive vaccines.

Humans↗
PubMed1998

Clinical safety evaluation of combination vaccines.

The development plan for new combination vaccines should include clinical studies designed to provide an adequate safety database (as well as efficacy data) to support licensure. Ideally, randomized studies to compare the safety of the combination vaccine with the separately administered components (or already licensed combinations of components) should be performed. For new combination vaccines having components with proven efficacy, comparative immunogenicity data may provide a sufficient basis to support efficacy, precluding the need for a large efficacy study. In the absence of the safety database that would have been derived from such an efficacy study, it is important to conduct a comparative safety study with a sample size suitable for the evaluation of less common adverse events. For large safety trials, a simplified design where only a subset of subjects is assessed in detail for the more common adverse events may be appropriate.

Biometry↗
PubMed1994

Deleterious effect of thimerosal on the potency of inactivated poliovirus vaccine.

High-potency inactivated poliovirus vaccine (eIPV) was combined with diphtheria-tetanus-pertussis (DTP) vaccine containing thimerosal as a preservative to simulate the performance of a potential tetravalent vaccine. Neither type 1 nor type 3 poliovirus antigens appeared to be affected by thimerosal after exposure for 1 h at 37 degrees C as measured by enzyme-linked immunosorbent assay (ELISA). One epitope on the type 2 antigen was damaged within 5 min of exposure; however, the overall potency was unchanged when measured using a polyclonal antibody preparation. Exposure to thimerosal at 37 degrees C decreased the potency of all three poliovirus types to well below the level caused by heat deterioration alone in 1-2 days and to 0% after 16-17 days. At 25 degrees C, the potency of type 1 poliovirus decreased by 46% in 1 day, whereas poliovirus types 2 and 3 were stable for 1 week. Storage of eIPV at 4 degrees C in the presence of thimerosal reduced the potency of type 1 poliovirus antigen to undetectable levels after 4-6 months. Type 2 and 3 antigens were less markedly affected by 8 months of exposure to thimerosal at 4 degrees C. The loss of potency of type 1 as measured by ELISA was paralleled by a reduced level of neutralizing antibodies in mice injected with these preparations. The results obtained from testing eIPV in combination with DTP and thimerosal were generally similar to those obtained using eIPV with thimerosal. It remains to be seen to what extent thimerosal will affect the immunogenicity of eIPV in humans when injected as combined eIPV-DTP vaccine.

Animals↗
PubMed1990

Statistical modeling of selected aspects of the childbearing process with application to World Fertility Survey countries.

"A mathematical model for estimation of certain aspects of the childbearing process, which requires only data on age-specific fertility rates, is developed. Synthetic maternal childbearing indices, namely, mean ages at first and last birth, length of reproductive life span, inter-birth spacing, and proportion of childless women, in addition to the well-known mean age at childbearing, for the WFS [World Fertility Surveys conducted in developing] countries are obtained using the proposed model. The indices are free from age truncation effects, and, under certain assumptions, provide information about a cohort's completed fertility before the women stop reproducing. The effects of women's residence and education on fertility are also examined." (SUMMARY IN FRE)

Age Factors↗
PubMed1986

A parity-specific fertility table for Egypt: application of Nour's method.

"In the present paper, a method of constructing a fertility table based on the observed current parity distribution, developed by Nour (1984), is used to obtain a parity-specific fertility [rate] for Egypt....Nour's method is based on the assumption that women at a given parity and age will have the same fertility behavior regardless of their previous experience." Data are from the 1980 Egyptian Fertility Survey.

Africa↗
PubMedDate not supplied

The span of reproduction in Egypt.

This study shows long reproductive spans to be associated with low levels of women's education, rural residence, remarriage, early marriage age, and high parity. Effects are statistically significant.

Adolescent↗