A systematic review of ethical issues in vaccine studies involving pregnant women.

BACKGROUND: Immunization during pregnancy can provide protection for mother and child. However, there have been only a limited number of studies documenting the efficacy and safety of this strategy. AIMS: To determine the extent and nature of subject matter related to ethics in maternal immunization by systematically documenting the spectrum of ethical issues in vaccine studies involving pregnant women. METHOD: We conducted a systematic literature review of published works pertaining to vaccine and therapeutic studies involving pregnant women through searches of PubMed, EMBASE, Web of Science, the Cochrane Database, and ClinicalTrials.gov. We selected literature meeting the inclusion criteria published between 1988 and June 2014. We systematically abstracted subject matter pertaining to ethical issues in immunization studies during pregnancy. Immunization-specific ethical issues were matched and grouped into major categories and subcategories. RESULTS: Seventy-seven published articles met the inclusion criteria. Published articles reported findings on data that had been collected in 26 countries, the majority of which were classified as high-income or upper-middle-income nations according to World Bank criteria. Review of these publications produced 60 immunization-specific ethical issues, grouped into six major categories. Notably, many studies demonstrated limited acknowledgment of key ethical issues including the rights and welfare of participants. Additionally, there was no discussion pertaining to the ethics of program implementation, including integration of maternal immunization programs into existing routine immunization programs. CONCLUSION: This review of ethical issues in immunization studies of pregnant women can be used to help inform future vaccine trials in this important population. Consistent documentation of these ethical issues by investigators will facilitate a broader and more nuanced discussion of ethics in immunization of pregnant women - offering new and valuable insights for programs developed to prevent disease in newborn children in low- and middle-income countries.

Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.

BACKGROUND: Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. METHODS: We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. RESULTS: Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). CONCLUSIONS: Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.

A systematic review of adverse events following immunization during pregnancy and the newborn period.

In 2013, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) requested WHO to develop a process and a plan to move the maternal immunization agenda forward in support of an increased alignment of data safety evidence, public health needs, and regulatory processes. A key challenge identified was the continued need for harmonization of maternal adverse event following immunization (AEFI) research and surveillance efforts within developing and developed country contexts. We conducted a systematic review as a preliminary step in the development of standardized AEFI definitions for use in maternal and neonatal clinical trials, post-licensure surveillance, and other vaccine studies. We documented the current extent and nature of variability in AEFI definitions and adverse event reporting among 74 maternal immunization studies, which reported a total of 240 different types of adverse events. Forty-nine studies provided explicit AEFI case definitions describing 35 separate types of AEFIs. We identified variability in how AEFIs were determined to be present, in how AEFI definitions were applied, and in the ways that AEFIs were reported. Definitions for key maternal/neonatal AEFIs differed on four discrete attributes: overall level of detail, physiological and temporal boundaries and cut-offs, severity strata, and standards used. Our findings suggest that investigators may proactively address these inconsistencies through comprehensive and consistent reporting of AEFI definitions and outcomes in future publications. In addition, efforts to develop standardized AEFI definitions should generate definitions of sufficient detail and consistency of language to avoid the ambiguities we identified in reviewed articles, while remaining practically applicable given the constraints of low-resource contexts such as limited diagnostic capacity and high patient throughput.

Implementation of an electronic fingerprint-linked data collection system: a feasibility and acceptability study among Zambian female sex workers.

BACKGROUND: Patient identification within and between health services is an operational challenge in many resource-limited settings. When following HIV risk groups for service provision and in the context of vaccine trials, patient misidentification can harm patient care and bias trial outcomes. Electronic fingerprinting has been proposed to identify patients over time and link patient data between health services. The objective of this study was to determine 1) the feasibility of implementing an electronic-fingerprint linked data capture system in Zambia and 2) the acceptability of this system among a key HIV risk group: female sex workers (FSWs). METHODS: Working with Biometrac, a US-based company providing biometric-linked healthcare platforms, an electronic fingerprint-linked data capture system was developed for use by field recruiters among Zambian FSWs. We evaluated the technical feasibility of the system for use in the field in Zambia and conducted a pilot study to determine the acceptability of the system, as well as barriers to uptake, among FSWs. RESULTS: We found that implementation of an electronic fingerprint-linked patient tracking and data collection system was feasible in this relatively resource-limited setting (false fingerprint matching rate of 1/1000 and false rejection rate of <1/10,000) and was acceptable among FSWs in a clinic setting (2% refusals). However, our data indicate that less than half of FSWs are comfortable providing an electronic fingerprint when recruited while they are working. The most common reasons cited for not providing a fingerprint (lack of privacy/confidentiality issues while at work, typically at bars or lodges) could be addressed by recruiting women during less busy hours, in their own homes, in the presence of "Queen Mothers" (FSW organizers), or in the presence of a FSW that has already been fingerprinted. CONCLUSIONS: Our findings have major implications for key population research and improved health services provision. However, more work needs to be done to increase the acceptability of the electronic fingerprint-linked data capture system during field recruitment. This study indicated several potential avenues that will be explored to increase acceptability.