New pediatric vaccine approved But why only now?

Dr. Rey D. Pagtakhan

	"Watch out, COVID-19"/ “Tiens-toi bien, COVID-19” – The Quebec government's ad campaign tries to get kids the vaccine by using humour. SOURCE: Quebec

On Friday November 19, Health Canada approved the pediatric formulation of Pfizer-BioNTech COVID-19 vaccine for kids 5 to 11 years of age. A momentous day, indeed!

It has been nearly a year since the adult version of the vaccine received emergency use authorization and about half-a-year since adolescents as young as 12 were added to the vaccine-eligible pool. Thus, we have reason to be thankful – a pediatric vaccine is finally available in the True North country.

But, why only now in Canada?

In fact, a similar question might also be asked: What took so long for the U.S. to grant its own approval to the pediatric vaccine? Hopefully, analysis of these questions would give our readers not only specific answers but also – and more importantly – a better understanding and appreciation of double-blind vaccine clinical trials, particularly in infants and children, their results and their value in helping us make informed decisions about their safety, efficacy and quality. Also, insights gained from consideration of these queries should help build trust and trustworthiness and motivate vaccine acceptance.

Importance of vaccine availability and perception of delay

First, let me summarize the observations that relate to the importance of the vaccine for kids 5 to 11 years of age and the implied concerns related to its non-availability:

1. Occurrence of new cases for most of the fourth pandemic wave has been highest in this specific age group;
2. Reduction in infection rates and outbreak-associated cases among older children aged 12 to 17 years following vaccination was notable;
3. Serious disease, including inflammation in the heart, lungs, and brain as well as long-term complications and deaths – although still less frequent than in adults – has occurred;
4. Infections within this age group increase intergenerational exposure;
5. Children in this age group congregate in large settings and events. Schools, day-care centres, celebrations, school work, team sports, and other social events are priorities for children, and they should not be hindered by fear of exposure or source of transmission;
6. Pandemic control measures have disproportionately adversely affected children’s physical, emotional, and mental well-being;
7. Waiting a significant period for a vaccine has amplified children’s lingering fears and continuing harms;
8. Reducing transmission reduces continuing circulation of the virus and emergence of variants of concern;
9. Increasing the total population pool of the vaccinated hastens attainment of community immunity; and
10. Immunizing this age group would help in eventually controlling the pandemic.

Second, let me summarize the reasons for a perception of preventable delay in having in Canada the pediatric vaccine for this age-specific group:

1. Canada and the world have had at least a two-year experience of success with the adult formulation, not only in adults but also in adolescents as young as 12, from clinical trials and surveillance data of real-world utilization;
2. It has already received full licensing approval for marketing the product with its brand name Comirnaty;
3. It has met the high standards required for evidence of safety, efficacy, and quality; and
4. It has widely received a high level of public confidence as reflected in its acceptance (per cent of vaccinated population).

So remarkably high was the level of confidence engendered that, reportedly, “some parents, pediatricians, and scientists (in the U.S.) began debating whether it could be administered “off-label.” That is, to administer a government-approved vaccine to another population age group in a different dosage such as to the much younger non-eligible kids than what it was approved for. Briefly considered, but the feasibility was swiftly cast aside. This was not surprising since the U.S. regulatory process is deemed the world’s strictest in granting emergency use authorization to new drugs and vaccines.

Likewise, the Canadian regulatory process is as strict and comprehensive as it is independent. Thus, it was equally not surprising that we experienced the nearly three-week delay from October 29 when the U.S. gave its initial green light to the pediatric formulation and November 2 when the approval process was fully completed to November 19 when Canada announced its own approval.

Understanding pediatric clinical trials

The science essay Why kids need their own COVID-19 vaccine trials by science writer Sarah Elizabeth Richards (National Geographic. February 19, 2021) and the vaccine blog When will children and adolescents be vaccinated against COVID-19? by Professors Anna Durbin, William Moss, Kawsar Talaat, and Ruth A. Karron (Department of International Health, Center for Immunization Research, and the International Vaccine Access Center. Johns Hopkins University Bloomberg School of Public Health and Medicine. Coronavirus Resource Center. February 25, 2021) jointly provide me with the backgrounder and references for my analysis of the question: Why only now in Canada for the Pfizer COVID-19 pediatric vaccine for kids 5-11?

Science writer Richards opened her essay with the story of librarian Megan Egbert and her two daughters ages 12 and 14 who promptly agreed, upon hearing about the recruitment drive for volunteers to join a COVID-19 vaccine clinical trial. While the daughters became instant “mini celebrities” in their school following their first jabs and were applauded by hundreds in the social media as “brave young ladies,” the mother received the message that she is “using the kids as guinea pigs…it’s not for teens until it’s been tested.”

This type of message illustrates the well-known puzzling question in doing clinical trials in children on medical drugs and vaccines. As Richards has aptly emphasized: “How can scientists know the vaccines are safe for children unless they test them on actual children? And if children can benefit from the vaccine and play an important role in establishing herd immunity, why have pharmaceutical companies waited to study them?

To this I add a related question: Why do vaccine manufacturers start their clinical trials in children, in contrast to adults, in staggered age groups (also called as “age de-escalation” strategy), starting with the adolescents (12 to 17 years of age) and gradually going to infancy (5 -11 years; 2-4 years; and 6 months – under 2 years)?

Children are not just small adults

Answers to these questions require an acknowledgment that children do have different body metabolism, as Professor Anna Durbin and her colleagues at Johns Hopkins University would like to remind us. Children’s development and maturity are ongoing processes.

Below is a list of reasons why children need their own clinical trials.

1. Foremost, government regulatory agencies as in Canada and the U.S. require that vaccines be independently studied in children for a number of reasons:
    a. Their immune systems are still maturing and may react to the COVID virus differently;
    b. They may have side effects or adverse reactions that do not occur in adults;
    c. They might respond better or worse; and
    d. They may need a child-specific formulation and dosage schedule unique to the different age-subgroups.

2. Also, researchers could build on the results obtained in adult study; that is, if proof of efficacy from studies in adults is solid, pediatric clinical trials could focus more on safety and immune response; thus, clinical trials may not require as large a study as in adults;

3. Clinical trials in children must be low risk and offer a clear potential for benefits, that is, kids ought to be protected from unnecessary risk. That is why, institutional research ethics committees are created and review research proposals for compliance with the principles and integrity of governing participation in pediatric clinical trials.

Pediatric clinical trials are more challenging

Frequent appointments for monitoring (interviews, blood tests), dutiful record-keeping of signs and symptoms that may or may not develop for many weeks and months, and telemedicine visits do impose a heavy burden on research participants. Their parents may require access to day-care centres and transportation, and may find it difficult to juggle their schedules between their jobs and research visits. Put all these together and you develop a clear picture of why pediatric clinical trials of vaccines can be most challenging. Although they are reimbursed for expenses, participants may not be paid except for a modest honorarium.

Indeed, both parents and children really need to connect with the research project. They need to develop a deep sense of “emotional connection” – a sense of purpose and altruism – to enrol and remain in the clinical trials. They really deserve our deep appreciation. And I am pleased to share, if I may, that I have been privileged to see participants’ altruistic engagement during my pre-retirement years.

Give children a say in vaccination

In its summary statement, the National Advisory Committee on Immunization (NACI. November 19, 2021) issued this guidance: “It is essential that children and their caregivers are supported and respected during the decision-making process, so they are able to make an informed decision about COVID19 vaccination.” (I discussed the formulation and related information about the new pediatric vaccine in my previous article – see Pilipino Expess / Medisina at Politika. Nov 16, 2021.)

The following day, Prime Minister Justin Trudeau echoed the same sentiment in his National Child Day statement. “Today, …we celebrate the rights of children, …We know that vaccines are one of the most effective ways to protect ourselves, our families, and our communities from COVID-19. Children under the age of 12 have waited patiently…now, children between the ages of five and 11 will be able to get vaccinated …the government will continue … to ensure parents and guardians are supported in making informed decisions on COVID-19 vaccination.”

Indeed, children want to have a say. They want to “be partners, not pawns,” as Canada continues its fight against the COVID-19 virus and its variants of concern.

Summation

Immunization is a story of medical success. The availability of the new Pfizer pediatric COVID-19 vaccine – the first ever approved in Canada – is a welcome addition to our public health tools to help control the pandemic. Immunization of children 5 to 11 years of age – the age group that has the highest occurrence rates of new COVID-19 cases for the most part of the pandemic fourth wave – is timely, indeed. Particularly as the newest variant of concern, Omicron, appears to be starting its global journey.

It took a while for the pediatric vaccine to make its way to Canada, in fact, even to the U.S. Now we understand and appreciate why the temporal route was long. Children must have their own independent clinical trials and only when the potential for benefits – to citizens and country – far outweigh the risks. That is, for an abundance of caution and care about our children whose say on matters that affect them shall be respected and protected.

Better understanding of the ethical principles governing clinical trials of vaccines and the rigorous requirements for safety, efficacy, and quality that must be met, and the subsequent review, recommendations, and guidance by NACI, all give parents and the children the basis for trust in the trustworthiness of this vaccine.

We understand, too, why only now we have the Pfizer pediatric COVID-19 vaccine in Canada.

Dr. Rey D. Pagtakhan, P.C., O.M., LL.D., Sc.D., M.D. M.Sc. is a retired lung specialist, professor of child health, author of articles and chapters in medical journals and textbooks, and a former health critic, Parliamentary Secretary to the Prime Minister, and cabinet minister, including Secretary of State for Science, Research and Development. He graduated from the University of the Philippines, did postgraduate training and studies at the Children’s Hospitals of Washington University in St. Louis and the University of Manitoba in Winnipeg, and spent a sabbatical year as Visiting Professor of Pediatrics at the University of Arizona Medical Center. In June 2003, he spoke on “The Global Threat of Infectious Diseases” at the G-8 Science Ministers/Advisors Carnegie Group Meeting in Berlin. Contact: reypagtakhan@gmail.com

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