As the coronavirus pandemic continues across the world, there has been a scramble to release a safe and effective vaccine.
Over 140 candidate vaccines have been developed globally, and 18 of them are currently in human trials.
Vaccine trials usually undergo three rounds of testing: phase 1, phase 2 and phase 3. The first two trials are typically smaller ones, testing mostly for vaccine safety and biological activity, requiring from 50 to hundreds of volunteers respectively. Due to their smaller size, it's relatively easy for pharmaceutical companies to run these studies in their home countries.
Comparatively, phase 3 trials are a lot more difficult, requiring thousands of volunteers to gauge whether the vaccine works in the real world.
"Most vaccine phase 3 trials need to enroll tens of thousands of patients. ... You need lots of people to show a statistically significant difference," said Dr. Todd Ellerin, the director of infectious diseases at South Shore Health.
As companies accelerate their research time frames, many have begun looking beyond their own borders, eying volunteers in places where the epidemic is still raging.
"You want to be able to test the efficacy of a vaccine in a country that has ongoing infections," said Dr. Paul Goepfert, the director of the Alabama Vaccine Research Clinic.
Although infections are occurring globally, they are not divided evenly at any given time. Now, companies from the U.K., China, South Korea and Germany -- countries where the pandemic is relatively under control -- are looking for new places to start their phase 3 studies.
According to the World Health Organization, only one candidate -- the U.K.'s University of Oxford, which is partnering with the pharmaceutical company AstraZeneca -- has officially launched a phase 3 trial.
The other front-runners include U.S.-based Moderna, Inovio and Pfizer, which is partnered with German biotech company BioNTech. China-based companies CanSino, Sinovac,and Sinopharm, are also gearing up for their own phase 3 trials in the coming months.
With the pandemic still spreading in the United States, American companies may not need to look abroad for their phase 3 studies. In fact, Moderna has announced it will begin a phase 3 trial on 30,000 participants within the U.S., beginning this July.
And a spokesperson for Inovio told ABC News that the company will not be testing its vaccine abroad, as "the infection rates in the U.S. are currently high and so we will be able to assess the efficacy of the vaccine in subjects in the U.S."
Pfizer, however, an American company partnering with German-based BioNTech, is looking to conduct global phase 3 trials, although the partners have not yet announced the sites where these trials would take place.
In contrast, U.K.'s Oxford COVID-19 vaccine will be evaluated not only in the U.K. but also in South Africa, the U.S., Brazil and India.
"The listed sites are a priority for the study because of the ascendant curve of the COVID-19," a representative from University of Oxford told ABC News.
Companies based in China, where the coronavirus is largely controlled, are also making similar plans to test their vaccines overseas.
China's Sinovac is preparing phase 3 trials in China and Brazil, while Sinopharm's phase 3 trial will be carried out in the United Arab Emirates. China's CanSino also looks to further test their vaccine overseas in Canada as well as in the Chinese military. However, the lower rates of circulating virus in Canada and UAE may cause challenges.
"In China now, the pandemic is basically well-controlled, so at least for now, no one can expect an optimal trial environment for the efficacy study," said a spokesperson for the Chinese biotech company Walvax, currently in the phase 1 stage of testing.
"Consequentially, we are likely to conduct the phase 3 clinical trial in countries where the population is large and the infected number is still on the rise," the spokesperson said.
Meanwhile, South Korea-based Genexine -- also in phase 1 -- has already set up collaborations with foreign parties including Indonesia, Thailand and Turkey for its forthcoming phase 2 trial. A spokesperson told ABC News that if the company were to move on to phase 3, it would also consider countries like the U.S., Brazil and Russia where large numbers of new COVID-19 cases occur.
As all these companies look to test their vaccines in citizens of countries with high infection rates of coronavirus, Ellerin warned that companies will have to find a way to not compete with each other, "so finding different parts of the globe to conduct these trials are key."
Apart from concerns over increased competition between companies, there are also concerns about how vaccines will be distributed if one does prove to be effective. Bioethicists warn that it may not be ethical to conduct studies in one county, but then prioritize vaccination for citizens of another country once the vaccine proves successful.
"Most countries who agree to test vaccines in their country do so with the provision that they will have access to the product if efficacy is seen," said Goepfert.
Vaccine developers have also explicitly voiced such intentions.
"We will spare no efforts to ensure that people who live in countries where a trial might be taking place will get equitable access to the vaccine," said a spokesperson for Walvax Biotech in China, for example.
A University of Oxford spokesperson told ABC News that it has made a commitment to equitable global access, although "decisions on who gets the vaccine first will be made by policymakers and are likely to focus on those with highest risk, including healthcare workers."
Interestingly, multinational pharmaceutical company GlaxoSmithKline is taking a different approach to help address the high global demand for an effective vaccine. They will supply their "pandemic adjuvant technology" to their numerous collaborating vaccine candidate companies.
The technology "may reduce the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and therefore contributing to protect more people." In addition, the company aims to make their adjuvant available to all countries, and will "offer donations ... to global institutions who can determine the need and help with delivery on the ground."
As the world looks for a solution to the COVID-19 pandemic, large vaccine trials are likely to be carried out in countries with a high and increasing infection rate. Currently, such countries include the U.S., Brazil, India and South Africa.
Because of the ethical concerns regarding such a setup for foreign vaccine testing, experts agree that it will take unprecedented levels of international collaboration for a swift production of an effective COVID-19 vaccine.
Hassal Lee, a neuroscience Ph.D. and student doctor at the University of Cambridge, is a contributor to the ABC News Medical Unit.