Meeting the Needs of Pregnant Women in the Zika Response: - PowerPoint Presentation

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Meeting the Needs of Pregnant Women in the Zika Response: Testing and Using a Live Vaccine in Pregnancy?

Carleigh Krubiner, PhDJohns Hopkins Berman Institute of BioethicsGlobal Forum on Bioethics in ResearchBuenos Aires, ArgentinaNovember 3, 2016

Funded

by Slide2

Introduction: The Zika EpidemicSince Fall 2015, Zika has rapidly spread across Latin America and beyondFebruary 1, 2016: Public Health Emergency of International ConcernOur initial suspicions and fears re: links to congenital malformations and neurological complications confirmed – worries deepening the more we learnSlide3

Zika Virus: What we “know” so farFlavivirus (dengue, chikungunya, yellow fever, etc.)Transmission: Mosquitoes, Sexual, Vertical, Blood, other?Zika in adults: generally mild, similar to seasonal flu, rash, conjunctivitis – 80% asymptomaticGBS, other neurological complicationsCongenital effects on fetus: CZS

Microcephaly and other neurological effectsOther malformations and abnormalities: ocular, musculoskeletalMost severe cases appear to be associated with 1st trimester infection - but emerging evidence suggests persistent risk throughout pregnancySlide4

The Zika Crisis: A Spotlight on PregnancyWe can’t ignore pregnancy in this epidemic – because it is at the crux of the most devastating outcomes associated with Zika infectionWe have to consider pregnant women in our response, and in the biomedical research that will drive and inform our efforts to address current crisis and future outbreaksBrings to the forefront a number of the ethical, legal and logistical challenges of doing research in pregnancy – compounded by the urgency of the PHE contextBut, also an opportunity to tackle various challenges, complexities, and preconceived notions that have stilted research with pregnant women in other health areasSlide5

Key Issue: Zika Vaccine ResearchSignificant investment in development of ZIKV vaccinesWhether, When and How to Include Pregnant Women?Slide6

Why we have to consider pregnant womenThere will be pregnant women in areas of active Zika transmission who will want and need interventions to protect themselves and their future offspringEmerging evidence that the constellation of adverse outcomes associated with congenital infection are not limited to 1st trimesterTrial participation can provide earlier access to investigational interventions with prospect for direct benefit

Lack of evidence in pregnancy can lead to exclusionary policies and practice once interventions are rolled out to the general public – even if risks seems minimal in pregnancy These women may be a greater risk of infection given sexual transmission and low condom use in pregnancySlide7

Why we have to consider pregnant womenWith women of childbearing age as the target population for a vaccine, likely to be many inadvertent exposures in pregnancyVaccine trials enrolling women of childbearing age: some will already be unknowingly pregnant and some will become pregnant

Even more will be exposed in rollout Data needed on safety to inform relevant care decisionsSlide8

Zika Vaccines in the PipelineSource: Durbin, 2016Slide9

Live Attenuated Vaccines Some of the most promising vaccine candidates – for the immediate and longer-term response – are live attenuated vaccinesLive vaccines tend to have certain comparative advantages:Often single dose – greater protective coverage, lower costLonger durability – protection in future pregnancies

Value-for-money proposition potentially greater – could be most likely platform adopted by gov’ts for their population level Zika responseWhat’s more, no guarantees that the other vaccine platforms being studied will prove efficaciousSlide10

Live Attenuated Vaccines in Pregnancy “Conventional Wisdom” - live vaccines historically contraindicated for use in pregnancyThis is due to the theoretical risk that a replication-competent vaccine could infect the fetus and cause harm Yet, from

our experience with other diseases, we have not seen any adverse outcomes due to the inadvertent use of live vaccines in pregnancy (e.g., Rubella, Yellow Fever, Polio)For YF and OPV, recommended use in pregnant women at high risk of exposure Slide11

Live Vaccines in Pregnancy: Worth Revisiting?Cons

Biologically plausible risk of infecting the fetusPotential risk of vaccine-induced GBS (unknown comparative risk)Safer alternatives may exist for pregnancyProsOften single dose, so may have greater protective coverageLonger durability – protection in future pregnanciesMay be cheaper and easier to administer than alternativesTo-date, have not seen ill-effects inadvertent exposures to live vaccines for other diseases

Unknown which platforms and candidates will prove efficacious – what if only live ones work?Slide12

Tough Questions on Live Vaccines in Pregnancy:Should pregnant women be allowed to participate in trials of live Zika vaccine candidates?If they live in an area of active Zika transmission where the background risk of infection is high?How to weigh risks/benefits of vaccination vs. wild-type infection?

How ought social justice considerations influence decisions to allow early access to potentially beneficial vaccines through trial participation?What conditions and considerations would justify prospective enrolment of pregnant women in live Zika vaccine trials?How would the relevant considerations compare/contrast to other types of public health emergencies/infectious diseases?What are the potential implications of not including pregnant women in live ZIKV vaccine research?Influence on future access to an efficacious live vaccine?Potential for misplaced fear and anxiety among pregnant women who are inadvertently given live vaccine in pregnancy?May lead to unnecessary terminations (e.g., rubella)Slide13

Tough Questions on Live Vaccines in Pregnancy:If pregnant women not included in trials, how can we ethically generate the best possible data on safety to inform relevant health care decisions? What can we learn from in vitro or animal studies?

What can we learn in the context of clinical trials?What can we learn from early roll-outs?What are the pros/cons of relying solely on data from animal models and inadvertent exposures, with regard to:Scientific Validity?Distributive justice?Potential harms associated with delayed evidence generation?Slide14

Tough Questions on Live Vaccines in Pregnancy:How can and should local context, norms, values, and culture – both among pregnant women and broader Zika-affected communities – shape and inform the ethics analyses for each of these questions?

Including, but not limited to:Access to and uptake of family planning and reproductive health servicesAccess to abortion servicesLocal conceptions of disability and available services for people living with disabilitiesRoles and shared decision-making among family membersGender norms as well as the potential for GBV and/or abandonmentSlide15

Many questions to tackle as we move forward with the Zika response – particularly R&D of live vaccinesWhat can we learn from our collective experiences – previous successes and failures?What can we learn from the Zika case for future emerging epidemics?

Beyond Zika, how and when ought we consider challenging the current dogma surrounding live vaccines in pregnancy - to best ensure pregnant women and their future offspring can benefit appropriately from biomedical advancements?Slide16

With generous funding support from the

Wellcome Trust