Vaccination under pessimistic expectations in clinical trials and immunization campaigns

• Published date: 01 December 2023
• Author: Hippolyte d'Albis,Johanna Etner,Josselin Thuilliez
• Date: 01 December 2023
• DOI: http://doi.org/10.1111/jpet.12617

Received: 11 February 2022

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Accepted: 21 August 2022

DOI: 10.1111/jpet.12617

ORIGINAL ARTICLE

Vaccination under pessimistic expectations in

clinical trials and immunization campaigns

Hippolyte d'Albis

1

|Johanna Etner

2

|Josselin Thuilliez

3

1

Paris School of Economics, CNRS, Paris,

France

2

EconomiX, UPL, Paris Nanterre

University, CNRS, Paris, France

3

CNRS—Centre d'Economie de la

Sorbonne, UMR8174, Université

Panthéon‐Sorbonne‐CNRS, Paris, France

Correspondence

Josselin Thuilliez, CNRS—Centre

d'Economie de la Sorbonne, UMR8174,

Université Panthé‐Sorbonne‐CNRS,

Paris, France.

Email: Josselin.Thuilliez@univ-paris1.fr

Abstract

We provide one of the first formalizations of a

vaccination campaign in a decision‐theoretic frame-

work. We analyze a model where an ambiguity‐averse

individual must decide how much effort to invest into

prevention in the context of a rampant disease. We

study how ambiguity aversion affects the effort and the

estimation of the vaccine efficacy in clinical trials and

immunization campaigns. We find that the behaviors

of individuals participating in a clinical trial differ from

individuals not participating. Individuals who are more

optimistic toward vaccination participate more in

trials. Their behaviors and efforts are also affected.

As a result, because vaccine efficacy depends on

unobserved behaviors and efforts, the biological effect

of the vaccine becomes difficult to evaluate. During the

scale‐up phase of a vaccination campaign, provided

that vaccine efficacy is established, we show that

vaccine hesitancy may still be rational.

1|INTRODUCTION

The coronavirus vaccines approved in Europe are considered as remarkably effective. Several

studies undertaken in real‐world conditions indicate that overall, COVID‐19 vaccination has

reduced the number of new SARS‐CoV‐2 infections, with the largest benefit received after

two vaccinations and for symptomatic and high viral burden infections (Chodick et al., 2021;

J Public Econ Theory. 2023;25:1188–1211.1188

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wileyonlinelibrary.com/journal/jpet

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits

use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or

adaptations are made.

© 2022 The Authors. Journal of Public Economic Theory published by Wiley Periodicals LLC.

Haas et al., 2021; Lustig et al., 2021; Milman et al., 2021; Pritchard et al., 2021). However, there

is continuing concern about vaccine hesitancy in some countries and some communities within

them (Kluge & McKee, 2021). Proving that a COVID‐19 vaccine is safe and effective can only be

a turning point if the uptake of the vaccine is high enough to stop the circulation of the virus

(Chevallier et al., 2021). Therefore, there is an urgent need to better understand how to reach

out to those who have the opportunity to be vaccinated but refuse to do so. Previous research

has identified several promising levers for reducing vaccine hesitancy. These include the

motivation to be altruistic (Shim et al., 2012), emphasis on the dangers of the disease (Horne

et al., 2015), rational calculation of pros and cons, and anticipated regret at not having been

vaccinated (Betsch et al., 2015; Brewer et al., 2016). However, analyzing cepticism about

vaccination is difficult, because of the critical issue of disentangling so many factors involved in

vaccination decisions.

In this paper, we provide one of the first formalizations of a vaccination campaign in a

decision‐theoretic framework. We build a model that can be used to compare self‐protection

and behaviors before a vaccine trial is implemented, during the trial and when immunization is

scaled‐up. In a nutshell, we analyze a model in which an ambiguity averse individual must

decide how much effort to invest in prevention in the context of a rampant disease. The

individual may decide to participate in a randomized vaccination clinical trial and later in a

vaccination campaign. The main objective is to study how ambiguity aversion affects the effort

exerted by the individual and the estimation of the vaccine efficacy. The model shows that

individuals participating in clinical trials behave differently than individuals not participating,

with behavioral differences owing to risk attitude. These differences may in turn compromise

the validity of the vaccine efficacy calculation. The paper also finds that vaccine hesitancy may

persist even if vaccination has beneficial effects. Specifically, our benchmark model in the

absence of a vaccine simply starts by showing that efforts (to invest in prevention) increase with

income and decrease with exogenous improvements in the probability of not developing a

severe form or dying from COVID‐19.

The extension of this simple model includes vaccination and adverse effects during a

clinical trial. As perceived adverse events may differ across individuals, we introduce a

certain degree of pessimism related to vaccination. We show that when individuals

participate in a clinical trial,themorepessimistictheyare,themoretheywillinvestin

prevention, whereas optimists make fewer efforts. This is indeed crucial in clinical trials as

informed participation is on a voluntary basis. Another consequence of voluntary

participation is that the utility of participating in a clinical trial is greater than not

participating. Clearly, this may depend on the health system. Participating in a trial may

mean access to free care in the United States, whereas in France, this type of motivation does

not exist. This may generate selection bias and also differential efforts between optimists and

pessimists in an endogenous way. Put differently, only people with relatively low pessimism

may participate in the trial. We show that the share of pessimists in the trial may in turn

affect vaccine efficacy. When the probability of catching COVID‐19 and the probability of

developing a severe form after being infected, are two independent features, we show that it is

indeed possible to identify the treatment (vaccine) effect. Otherwise, the treatment effect

remains undetermined. Whether these events are independent is debatable (Chidambaram

et al., 2020;Izcovichetal.,2020;Liuetal.,2020;Pijlsetal.,2021;Rozenfeldetal.,2020).

There are probably some joint confounding factors and the availability and evolution of

screening guidelines, individual factors, or clinical judgment may also affect who is tested

(Rozenfeld et al., 2020).Theamountofevidenceremainslimitedonthisquestion,though

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