Adam F. Cohen|Joop van Gerven|Juan García Burgos|Anthonius de Boer|Ron A. M. Foucher|H. Flore|Zvi Teitelbaum|Willem van Eden|David J. Webb|Serge Cremers
COVID?19 vaccines: the importance of transparency and fact?based education
Centre for Human Drug Research|Leiden University|European Medicines Agency|Utrecht University|Erasmus MC|HAL Allergy (Netherlands)|Rambam Health Care Campus|Utrecht University|King's College London|Columbia University
one 1601 vaccines sarscov2 virus currently development shown sufficiently safe effective largest vaccination campaign ever hopefully contribute extract world current crisis take place midst rising vaccine hesitancy sentiments many parts world addition engraft challenges due called vaccine development pandemic speed2 transparency key public trust old normality becomes relevant confronted unprecedented paradigm vaccine development vaccine development always establishment link working neutralizing antibody response specific cell development helping prevention disease population base acceptable safety profile although standards benefit risks medicines routes development assessment however stretched limit view public health emergency facing sarscov2 already killed humans hiv measles together year3 4 produced economic societal damage cause negative effects years come also worldwide public health enormity crisis also led extraordinary effort find treatments ranging immunomodulators antivirals hyperimmune serums include success date dexamethasone5 remdesivir6 widely used clinical practice covid19 patients 6 months discovery disease preventing disease community spread via mass vaccination generally assumed best way crisis realization led 1601 vaccines developed parallel several published papers report vaccines shown work preclinical early phase clinical trials79 regard neutralizing antibody formation protection induced disease animals confirmed regulatory assessment would major accomplishment especially rapid development process line guidelines vaccine development1012 trials evaluate vaccines safety efficacy ongoing performed level public scrutiny understandably beyond usual public interest drug development puts severe stress system previously proceeded much steadier rate many voices underlining importance releasing vaccines proven effective safe however important nuance meant safe perceived public often assume safe implies side effects difficulty conveying messages around vaccines benefits risks fact general statements without qualification proper explanation help thus particularly important increase public understanding risks inherent medicines vaccine 100 effective preventing disease 100 safe vaccinated people despite need build public understanding consensus benefits vaccines unquestionable one considers example made eradication smallpox possible almost completely achieved polio trials 3050000 volunteers unable detect certain vaccinerelated adverse drug reactions adr rare serious common adverse reactions vaccines occurring 1 100 people mostly local well known shortlived side effects regarded synonymous adverse event adverse reaction event occurs treatment may intercurrent eventillness related preexisting condition adverse drug reaction adverse events rare post vaccination causal relationship vaccination difficult impossible determine events occur spontaneously also unvaccinated people therefore coincidental way determined clinical trials statistically reliable assessment number events following vaccination versus number events similar nonvaccinated population unlikely expected incidences events size phase iii trials first news relevant adverse effect covid19 vaccine trial occurred early september 2020 global trials chimpanzee adenovirusvectored vaccine chadox1 ncov19 azd 122213 temporarily paused neurological adverse effect disclosed media transverse myelitis produced headlines globe trials countries restarted without clear explanation sponsors communications sparse left scientific community general public behind uninformed confused nature event caused trial first stopped rapidly resumed transverse myelitis immunemediated polyneuropathies guillainbarr syndrome associated vaccination rare diseases respective incidences general population around 15 1118 per million per year low incidences hundreds thousands observations would required detect modestly increased risks vaccination examples guillain barre listed eu prescribing information adverse events detected postmarketing frequency cannot estimated available postmarketing data14 postvaccination autoimmune events plausible also occur infections guillainbarr syndrome described covid19 outbreak italy15 addition demonstration causality prolonged investigation extended periods shown possible association vaccine h1n1 influenza narcolepsy scandinavian countries 200916 knowledge occurrence rare adverse event stage transverse myelitis entirely unexpected cannot attributed confidence vaccine question adverse event enough reason stop enrollment interrupting trial would warranted event could change riskbenefit balance trial participants found related vaccination case may necessary temporarily interrupt trial analyze event obtain certainty causality introduce additional measures examine deal possibility mitigate risks future trial participants adverse events rapidly understood line drugs mechanism action likely attributable chance underlying disease associated conditions incidental cases adverse events also occur spontaneously rarely lead unexpected interruptions causality vaccination resolved comparison incidence control group treated group like trial number cases must sufficiently high take decision situations independent data safety monitoring committees place frequent access unblinded data make decisions camera avoid unblinding study researchers others prevent uncoordinated communication however compelling reasons transparent adverse effects new vaccines several covid19 vaccines currently development also make use adenoviral vector serious unexpected reactions occur one vaccine could also relevant agents class moreover analysis aggregate side effects adenoviral vector population versus rna vaccines could scientific interest information currently considered proprietary different companies unlikely shared conclude timely effective communication transparent handling cases like single event essential reinforce level trust system current development speed expected first mass vaccination start coming months parts world success vaccination campaign ultimately billions people across globe fully dependent trust transparency clear information regulatory authorities pharmaceutical companies covid19 vaccine development approval safety monitoring pivotal enabling trust whatever happens medical scientific community also required inform patients general public message must consistent informed good information materials educational programs general public start soon possible parallel scientific community need well informed able maintain trust essential component vaccine helps strongly reducing incidence disease without serious safety issues rather works producing immune response even vaccine works helps value uptake vaccine general population sufficiently high many younger people low risk dying covid19 infection 110000 1 10000017 therefore clear truthful proactive representation possibility serious complications may causally related coincidental essential context eu regulators taking step increasing level transparency covid19 medicines particular covid19 medicines european medicines agency ema publish full product information details conditions use scientific opinion adopted even formal marketing authorisation granted addition publication full epar european public assessment report made available within 3 days authorisation european commission furthermore clinical data submitted ema support applications covid19 medicines well full risk management plan assessment emas scientific committees subsequent commission decision published however scientific regulatory transparency automatically translate public confidence much broader educational effort necessary increased transparency parties academic institutions regulators commercial participants governments support make global research efficient allow public scrutiny independent review academics medical public health authorities ultimately every effort open data public scrutiny attract people right sources information help increase vaccine science literacy rather leaving void obscure theories propagate one lessons learned 2009 pandemic need internationally coordinated vaccine safety infrastructure safety pandemic vaccines rapidly deployed large numbers rapidly evaluated know another pandemic coming know challenge dealing medical complications current pandemic academic clinicians regulators scientists duty inform teach addition care hopefully prevent well cure competing interests declare