How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation?

Christine Stabell Benn*, Ane Bærent Fisker, Andreas Rieckmann, Aksel Karl Georg Jensen, Peter Aaby

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Publikation: Bidrag til tidsskriftReviewForskningpeer review

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Resumé

Introduction: Emerging evidence suggests that vaccines, in addition to their disease-specific effects, have important non-specific effects (NSEs), which contribute to their overall effect on mortality and morbidity. Immunological studies have shown that NSEs are biologically plausible. Many advocate that randomized controlled trials (RCTs) with overall mortality or morbidity as the outcome are the only way forward to confirm or refute NSEs. Areas covered: We discuss the limitations of using RCTs only as a tool to evaluate NSEs of vaccines. Such RCTs can be ethically problematic, they are time consuming and expensive. Furthermore, they only assess the NSEs in a given context, but it is inherent in the concept of NSEs that the NSEs of a given vaccine are modified by other immunomodulatory conditions. As an alternative, we propose that triangulation of RCTs and observational studies, merging multiple lines of evidence with different underlying bias structures, can build a strong argument for causality. We examine two examples related to measles vaccine and oral polio vaccine. Expert commentary: Using RCTs alone to evaluate NSEs of vaccines severely limits the possibilities for studying NSEs. Results from both RCTs and non-RCT studies should be triangulated to strengthen causal interpretation.

OriginalsprogEngelsk
TidsskriftExpert Review of Vaccines
Vol/bind17
Udgave nummer5
Sider (fra-til)411-420
ISSN1476-0584
DOI
StatusUdgivet - maj 2018

Fingeraftryk

Randomized Controlled Trials
Causality

Citer dette

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abstract = "Introduction: Emerging evidence suggests that vaccines, in addition to their disease-specific effects, have important non-specific effects (NSEs), which contribute to their overall effect on mortality and morbidity. Immunological studies have shown that NSEs are biologically plausible. Many advocate that randomized controlled trials (RCTs) with overall mortality or morbidity as the outcome are the only way forward to confirm or refute NSEs. Areas covered: We discuss the limitations of using RCTs only as a tool to evaluate NSEs of vaccines. Such RCTs can be ethically problematic, they are time consuming and expensive. Furthermore, they only assess the NSEs in a given context, but it is inherent in the concept of NSEs that the NSEs of a given vaccine are modified by other immunomodulatory conditions. As an alternative, we propose that triangulation of RCTs and observational studies, merging multiple lines of evidence with different underlying bias structures, can build a strong argument for causality. We examine two examples related to measles vaccine and oral polio vaccine. Expert commentary: Using RCTs alone to evaluate NSEs of vaccines severely limits the possibilities for studying NSEs. Results from both RCTs and non-RCT studies should be triangulated to strengthen causal interpretation.",
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How to evaluate potential non-specific effects of vaccines : the quest for randomized trials or time for triangulation? / Benn, Christine Stabell; Fisker, Ane Bærent; Rieckmann, Andreas; Jensen, Aksel Karl Georg; Aaby, Peter.

I: Expert Review of Vaccines, Bind 17, Nr. 5, 05.2018, s. 411-420.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - How to evaluate potential non-specific effects of vaccines

T2 - the quest for randomized trials or time for triangulation?

AU - Benn, Christine Stabell

AU - Fisker, Ane Bærent

AU - Rieckmann, Andreas

AU - Jensen, Aksel Karl Georg

AU - Aaby, Peter

PY - 2018/5

Y1 - 2018/5

N2 - Introduction: Emerging evidence suggests that vaccines, in addition to their disease-specific effects, have important non-specific effects (NSEs), which contribute to their overall effect on mortality and morbidity. Immunological studies have shown that NSEs are biologically plausible. Many advocate that randomized controlled trials (RCTs) with overall mortality or morbidity as the outcome are the only way forward to confirm or refute NSEs. Areas covered: We discuss the limitations of using RCTs only as a tool to evaluate NSEs of vaccines. Such RCTs can be ethically problematic, they are time consuming and expensive. Furthermore, they only assess the NSEs in a given context, but it is inherent in the concept of NSEs that the NSEs of a given vaccine are modified by other immunomodulatory conditions. As an alternative, we propose that triangulation of RCTs and observational studies, merging multiple lines of evidence with different underlying bias structures, can build a strong argument for causality. We examine two examples related to measles vaccine and oral polio vaccine. Expert commentary: Using RCTs alone to evaluate NSEs of vaccines severely limits the possibilities for studying NSEs. Results from both RCTs and non-RCT studies should be triangulated to strengthen causal interpretation.

AB - Introduction: Emerging evidence suggests that vaccines, in addition to their disease-specific effects, have important non-specific effects (NSEs), which contribute to their overall effect on mortality and morbidity. Immunological studies have shown that NSEs are biologically plausible. Many advocate that randomized controlled trials (RCTs) with overall mortality or morbidity as the outcome are the only way forward to confirm or refute NSEs. Areas covered: We discuss the limitations of using RCTs only as a tool to evaluate NSEs of vaccines. Such RCTs can be ethically problematic, they are time consuming and expensive. Furthermore, they only assess the NSEs in a given context, but it is inherent in the concept of NSEs that the NSEs of a given vaccine are modified by other immunomodulatory conditions. As an alternative, we propose that triangulation of RCTs and observational studies, merging multiple lines of evidence with different underlying bias structures, can build a strong argument for causality. We examine two examples related to measles vaccine and oral polio vaccine. Expert commentary: Using RCTs alone to evaluate NSEs of vaccines severely limits the possibilities for studying NSEs. Results from both RCTs and non-RCT studies should be triangulated to strengthen causal interpretation.

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KW - child mortality

KW - evaluation

KW - non-specific effects

KW - observational studies

KW - randomized controlled trials

KW - triangulation

KW - vaccine policy

KW - Vaccines

KW - Vaccines/administration & dosage

KW - Bias

KW - Humans

KW - Randomized Controlled Trials as Topic/methods

KW - Poliovirus Vaccine, Oral/administration & dosage

KW - Vaccination/methods

KW - Measles Vaccine/administration & dosage

KW - Immunity, Heterologous/immunology

KW - Research Design

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DO - 10.1080/14760584.2018.1471987

M3 - Review

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VL - 17

SP - 411

EP - 420

JO - Expert Review of Vaccines

JF - Expert Review of Vaccines

SN - 1476-0584

IS - 5

ER -