Methods for comparing durability of immune responses between vaccine regimens in early-phase trials

The ability to produce a long-lasting, or durable, immune response is a crucial characteristic of many highly effective vaccines. A goal of early-phase vaccine trials is often to compare the immune response durability of multiple tested vaccine regimens. One parameter for measuring immune response durability is the area under the mean post-peak log immune response profile. In this paper, we compare immune response durability across vaccine regimens within and between two phase I trials of DNA-primed HIV vaccine regimens, HVTN 094 and HVTN 096. We compare four estimators of this durability parameter and the resulting statistical inferences for comparing vaccine regimens. Two of these estimators use the trapezoid rule as an empirical approximation of the area under the marginal log response curve, and the other two estimators are based on linear and nonlinear models for the marginal mean log response. We conduct a simulation study to compare the four estimators, provide guidance on estimator selection, and use the nonlinear marginal mean model to analyze immunogenicity data from the two HIV vaccine trials.

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Evaluating the surrogacy of multiple vaccine-induced immune response biomarkers in HIV vaccine trials

Biostatistics ◽

10.1093/biostatistics/kxz039 ◽

2019 ◽

Author(s):

Sayan Dasgupta ◽

Ying Huang

Keyword(s):

Immune Response ◽

Vaccine Trial ◽

Hiv Vaccine ◽

Clinical Endpoints ◽

Hiv Vaccine Trials ◽

Marker Selection ◽

Vaccine Trials ◽

Potential Marker ◽

Potential Biomarker ◽

Response Biomarkers

Summary Identifying biomarkers as surrogates for clinical endpoints in randomized vaccine trials is useful for reducing study duration and costs, relieving participants of unnecessary discomfort, and understanding vaccine-effect mechanism. In this article, we use risk models with multiple vaccine-induced immune response biomarkers to measure the causal association between a vaccine’s effects on these biomarkers and that on the clinical endpoint. In this setup, our main objective is to combine and select markers with high surrogacy from a list of many candidate markers, allowing us to get a more parsimonious model which can potentially increase the predictive quality of the true markers. To address the missing “potential” biomarker value if a subject receives placebo, we utilize the baseline immunogenicity predictor design augmented with a “closeout placebo vaccination” group. We then impute the missing potential marker values and conduct marker selection through a stepwise resampling and imputation method called stability selection. We test our proposed strategy under relevant simulation settings and on (partially simulated) biomarker data from a HIV vaccine trial (RV144).

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Participation in two phase II prophylactic HIV vaccine trials in the UK

Vaccine ◽

10.1016/j.vaccine.2008.03.039 ◽

2008 ◽

Vol 26 (23) ◽

pp. 2919-2924 ◽

Cited By ~ 8

Author(s):

Kimberly Gray ◽

K. Legg ◽

A. Sharp ◽

N. Mackie ◽

F. Olarinde ◽

...

Keyword(s):

Phase Ii ◽

Hiv Vaccine ◽

Two Phase ◽

Hiv Vaccine Trials ◽

Vaccine Trials ◽

The Uk

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Developing countries to decide on HIV vaccine trials

Inpharma Weekly ◽

10.2165/00128413-199409610-00005 ◽

1994 ◽

Vol &NA; (961) ◽

pp. 5 ◽

Cited By ~ 1

Author(s):

&NA;

Keyword(s):

Developing Countries ◽

Hiv Vaccine ◽

Hiv Vaccine Trials ◽

Vaccine Trials

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A qualitative assessment of perspectives on the inclusion of adolescents in HIV vaccine trials in South Africa

International Journal of STD & AIDS ◽

10.1258/ijsa.2009.008484 ◽

2010 ◽

Vol 21 (3) ◽

pp. 172-176 ◽

Cited By ~ 9

Author(s):

H B Jaspan ◽

N F Soka ◽

C Mathews ◽

A J Flisher ◽

D Mark ◽

...

Keyword(s):

South Africa ◽

Hiv Vaccine ◽

Qualitative Assessment ◽

Hiv Vaccine Trials ◽

Vaccine Trials

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Willingness to participate in HIV vaccine research in a peri-urban South African community

International Journal of STD & AIDS ◽

10.1258/095646206775809259 ◽

2006 ◽

Vol 17 (3) ◽

pp. 176-179 ◽

Cited By ~ 17

Author(s):

J Smit ◽

K Middelkoop ◽

L Myer ◽

S Seedat ◽

L-G Bekker ◽

...

Keyword(s):

South African ◽

Hiv Vaccine ◽

Sub Saharan Africa ◽

Willingness To Participate ◽

Vaccine Research ◽

Substantial Impact ◽

Hiv Vaccine Trials ◽

Vaccine Trials ◽

Urban South ◽

African Community

Research on willingness to participate in HIV vaccine trials is important in preparations for HIV vaccine research, but there are few data from sub-Saharan Africa. We interviewed 198 individuals in a peri-urban South African community immediately after enrolment into an HIV vaccine preparedness study on their willingness to participate in hypothetical vaccine trials. Overall 23% of participants ( n = 46) said that they would be willing to participate in an HIV vaccine trial. Willingness was associated with increasing age, male gender, and increasing knowledge about vaccines generally and HIV vaccines specifically. In multivariate analysis, a 1-unit increase in HIV vaccine knowledge score was associated with a 10-fold increase in willingness to participate (adjusted odds ratio, 10.72, 95% confidence intervals: 4.40–26.12). These results suggest that while willingness to participate in HIV vaccine trials is relatively low in this setting, educational campaigns may have a substantial impact on individuals' willingness to participate in research.

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Contraceptive Use in Women Enrolled into Preventive HIV Vaccine Trials: Experience from a Phase I/II Trial in East Africa

PLoS ONE ◽

10.1371/journal.pone.0005164 ◽

2009 ◽

Vol 4 (4) ◽

pp. e5164 ◽

Cited By ~ 15

Author(s):

Hannah Kibuuka ◽

David Guwatudde ◽

Robert Kimutai ◽

Lucas Maganga ◽

Leonard Maboko ◽

...

Keyword(s):

Phase I ◽

East Africa ◽

Contraceptive Use ◽

Hiv Vaccine ◽

Hiv Vaccine Trials ◽

Vaccine Trials

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“Why Don’t You Go Into Suburbs? Why Are You Targeting Us?”: Trust and Mistrust in HIV Vaccine Trials in South Africa

Journal of Empirical Research on Human Research Ethics ◽

10.1177/1556264618804740 ◽

2018 ◽

Vol 13 (5) ◽

pp. 525-536 ◽

Cited By ~ 4

Author(s):

Siyabonga Thabethe ◽

Catherine Slack ◽

Graham Lindegger ◽

Abigail Wilkinson ◽

Douglas Wassenaar ◽

...

Keyword(s):

Vaccine Trial ◽

Hiv Vaccine ◽

Community Advisory Board ◽

Future Research ◽

Community Members ◽

Group Discussions ◽

Hiv Vaccine Trials ◽

Vaccine Trials ◽

Community Stakeholders ◽

Site Staff

Trust is a key element of high-quality stakeholder relations, which are themselves essential for the success of HIV vaccine trials. Where trust is absent, community stakeholders might not volunteer to become involved in key trial activities, and potential participants might not volunteer for enrollment. We explored site staff and Community Advisory Board (CAB) members’ experiences of trust/mistrust among community members and potential participants. We analyzed 10 focus group discussions with site staff and CAB members at two active South African HIV vaccine trial sites. We report on key characteristics perceived to contribute to the trustworthiness of communicators, as well as factors associated with mistrust. Attributes associated with trustworthy communicators included shared racial identity, competence, and independence (not being “captured”). Key foci for mistrust included explanations about site selection, stored samples, vaccination, and Vaccine Induced Sero-Positivity (VISP). Our findings suggest that community members’ trust is not necessarily global, in which trials are trusted or not; rather, it appears fairly nuanced and is impacted by various perceived attributes of communicators and the information they provide. We make recommendations for clinical trial site stakeholders invested in building trust and for future research into trust at these sites.

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