This is how we ensure the safety of a vaccine

Apr 07, 2015


John Donnelly
Director of the Vaccine Development Program at PATH

To ensure a vaccine is safe and effective, it must be carefully studied in the laboratory and go through several rigorous phases of clinical trials. If safety is not assured at any point, the vaccine candidate simply does not advance. Photo: PATH/Gabe Bienczycki.

You may not know that the DefeatDD team is housed within PATH's Vaccine Development Global Program, since our diarrheal disease advocacy originated with rotavirus vaccines. Today, we advocate for an integrated approach, including other vaccines against diarrheal disease that are on the horizon. Here, John Donnelly, director of our Vaccine Development Program, describes the rigorous research that goes into ensuring a vaccine's safety and efficacy. This post was originally featured on the PATH blog.

Before a drop of an oral immunization reaches a newborn's mouth or a syringe delivers a first shot, vaccines have cleared a multitude of hurdles, each carefully designed to ensure that they are safe and effective.

“It takes a village to raise a child,” the saying goes, and one of the first instances of collective care a child receives is immunization. Bringing a vaccine through research and into the clinic or field takes a veritable village of scientists, experts, and ethicists, and a rigorous process that ensures they collaborate at the highest standards.'From the initial stages of early research and clinical development through regulatory approval and use, vaccines are painstakingly evaluated for safety and efficacy.' -John Donnelly

My role as director of theVaccine Development Program at PATH, and a long career in vaccine research and development, have afforded me valuable insight on the need for vaccines throughout the world and the commitment of scientists in making sure vaccines safely protect our children.

From the initial stages of early research and clinical development through regulatory approval and use, vaccines are painstakingly evaluated for safety and efficacy. By the time a physician prepares an injection and administers it to stimulate a child's immune system, the vaccine contained within has been carefully studied in the laboratory and through several phases of clinical trials.

Each phase builds on the information received from the previous one, and if safety is not assured at any point, the vaccine candidate simply does not advance.

PATH and our partners led an 11-year effort to turn a little-known vaccine from China into an internationally approved tool to fight Japanese encephalitis. By 2017, the JE vaccine is expected to reach nearly 290 million people—a turning point in the battle to protect children from this dreaded disease. Photo: PATH/Satvir Malhotra.

On the journey to impact: the role of independent reviewers

A girl watches a health worker prepare a vaccination.

In 2014, children in Laos were vaccinated against Japanese encephalitis after the vaccine received World Health Organization approval earlier that year. Photo: PATH/Aaron Joel Santos.

A trial's researchers aren't the only ones to evaluate vaccine safety: expert, independent advisors make pivotal contributions throughout.

Ethical committees, independent safety review boards, and regulatory agencies—among these the US Food and Drug Administration and its counterparts in other countries—must approve a trial's design before it commences.

Each trial incorporates multiple levels of oversight to ensure the safety of its subjects. These groups join safety monitors and local community advisors in routinely checking standards, ensuring informed consent, and reviewing data collection. They evaluate all reported adverse events, both expected and unexpected, their severity and frequency, and whether such events call for halting the trial.

People gather around a table at the MenAfriVac vaccine launch in Burkina Faso.

In Burkina Faso, people line up for a dose of MenAfriVac®, the vaccine that targets the strain of bacterial meningitis that causes deadly epidemics throughout the 25-country African “meningitis belt.” To date, not a single case of meningitis A has been reported among the more than 215 million people who have been vaccinated. Photo: PATH/Gabe Bienczycki.

Defining impact: affordable, safe, and effective for all children

Adolescent girls gather to receive the HPV vaccination.

Clinical trials have proven that HPV vaccines are safe and nearly 100 percent effective against most cancer-causing types of HPV, as long as girls and young women are vaccinated before they've been exposed to the virus. Photo: PATH/Will Boase.

From this village of scientists and experts, ultimately we derive our intended impact—affordable, safe and effective vaccines for all children around the world, and particularly those in villages themselves: rural communities where the luxuries of our everyday lives aren't available to help keep kids healthy.

In communities where safe drinking water, access to routine health care, or appropriate nutrition are beyond reach, immunization may be the only health intervention that is both affordable and effective. Even today, children are suffering needlessly from diseases that we know vaccines can prevent. With infectious diseases like polio, measles, and Haemophilus influenzae type b all but eradicated in the US, many have forgotten how threatening and devastating they can be.

A mistaken interpretation of the risks and benefits of vaccination may lead some parents to incorrectly conclude that the vaccines themselves pose a greater risk than the diseases they prevent. When vaccines spare us from fear of disease—a reassurance that can too easily lead to complacency—lack of attention to vaccination can allow the diseases to return, causing needless illness and death.

Health worker giving a child a vaccine, while the child leans against a woman.

Where families have access to vaccines, children have a good chance at surviving common illnesses—growing, thriving, and eventually protecting their own children from preventable diseases. Photo: PATH/Gabe Bienczycki.

Value of vaccines: a global view

Where pneumonia, diarrhea, measles, influenza, and other vaccine-preventable diseases are still viewed as a common, lethal threats, the promise of vaccines takes on vital value and priority among families.

And for those who graciously participate in vaccine trials, researchers provide comprehensive information when requesting their consent for enrollment and sharing background about the disease, the vaccine candidate and manufacturer, risks, benefits, and how the clinical trial will be conducted.When our team and partners select clinics and communities to participate in large vaccine field trials—culminating steps in the long process to demonstrate safety and efficacy—we find that parents are eager to help investigate a vaccine that could literally mean the difference between life and death.

The science continues

After clinical trials, once a vaccine has demonstrated appropriate safety and significant potential for preventing disease, after it is licensed and put into practice, the science continues.

A health worker stands in the back of a truck with vaccine supplies.

PATH technologies often play a critical role in the supply chain—from the vaccine vial monitor that indicates the potency of a vaccine, to refrigeration and temperature-monitoring technologies that support its safe transport. Photo: PATH/Aaron Joel Santos.

Effectiveness studies allow us to see direct real-world impact as well as the value of herd immunity, which emphasizes the urgency to immunize children eligible for vaccination to better protect those who cannot be vaccinated because they are too young or their immune systems are compromised.

Routine surveillance shows us how well vaccines perform but also how rapidly risk can rise when families forego immunization.

Manufacturers and public health authorities monitor the experience of many thousands of children over many years to identify adverse events that are potentially related to vaccination but so rare that they may never appear in clinical trials. Ongoing evaluations of these very rare adverse events occurring in both vaccinated and unvaccinated populations, together with other data collected in post-marketing studies, enable us to further define vaccines' real-world risk/benefit ratio.

Clinical studies are crucial steps along the journey to make sure that every child is protected from vaccine-preventable diseases. Careful study allows PATH and our partners to ensure that new vaccines are safe and effective and ultimately close gaps in access to lifesaving immunizations.

By also strengthening health systems, accelerating research and development, and creating innovative technology solutions, PATH is working to make safe and effective vaccines affordable and available to all families.