With phase III COVID-19 vaccine trials each enrolling 30,000 participants or more in the U.S. and randomizing half of them to a placebo arm, only 150 incidents of the coronavirus infection are needed in a trial to show if the vaccine is at least 50% effective, NIH Director Francis Collins testified at a Senate Health, Education, Labor and Pensions (HELP) Committee hearing Sept. 9.
That’s why he’s cautiously optimistic a vaccine could be proved safe by the end of the year, Collins said.
Surgeon General Jerome Adams echoed Collins’ optimism and his insistence that science will drive any approval of a vaccine. The COVID-19 vaccine trials aren’t about time, Adams said. They’re about events. The size of the trials, which is 10 times greater than the 3,000 enrollment the FDA generally recommends for vaccines, allows investigators to identify safety and efficacy signals much sooner, he added.
“There will be no shortcuts. This vaccine will be safe. It will be effective, or it won’t be moved along,” Adams said.
Collins also assured the committee, “I can’t say strongly enough that the decisions about how this vaccine is going to be assessed will be based solely on science.” He explained some of the steps being taken to speed development without sacrificing the science – or safety and efficacy.
For instance, using a master protocol for all the vaccine trials saves time that would have been spent in the review of individual protocols. And scaling up manufacturing parallel to the development of the vaccines rather than following the traditional linear route that waits until a candidate demonstrates efficacy and safety is another timesaver.
While answering the need for urgency, that parallel development may be costly for both the government and biopharma companies. If a vaccine candidate doesn’t work or isn’t safe, all the doses that already have been manufactured and bought will have to be discarded, Collins said.
The urgency also means there’s no time to develop the “perfect” vaccine – one that would require only one dose and that could be stored at room temperatures, Collins said. All but one of the six candidates in development in the U.S. would require two doses, spaced 21 or 28 days apart. And Pfizer Inc.’s candidate would have to be stored at -70 degrees Celsius, Collins said. That requirement could make distribution of the vaccine, if it’s approved, difficult, as many facilities don’t have subzero storage capabilities.
Regardless of such challenges, safety “is foremost in all our minds. We cannot compromise here,” Collins said. As an example of that safety, he cited the hold Astrazeneca plc placed on its vaccine trial Sept. 8 because of an unexpected incident of what appears to be transverse myelitis that may, or may not, be related to the vaccine.
While developing a vaccine in the midst of a novel pandemic is challenging, the bigger challenge may be building public trust in the vaccine. The World Health Organization has listed vaccine hesitancy as one of the top 10 public health threats facing the world, Adams told the committee. In the U.S., that threat has increased in the midst of this year’s political campaign, he said.
He assured the committee there has been no political interference in developing a vaccine to take on the SARS-CoV-2 virus. But that didn’t stop the accusations. Several Democratic senators questioned the process, with a few recommending that groups other than the FDA should review the data as well before a vaccine is approved.
Expressing their own distrust, some used much of their five minutes of questioning Adams and Collins to blame President Donald Trump for the lack of trust in a future vaccine, saying his oft-repeated hope that a vaccine would be ready before the November election suggests that he will pressure the FDA to approve a vaccine before one has been adequately tested.
Sen. Elizabeth Warren (D-Mass.) cited a recent poll that found only 21% of Americans surveyed said they would be willing to get a COVID-19 vaccine if one were available this year. She blamed that hesitancy on the president, and Republicans in general, and tried to pressure Collins into agreeing with her.
His response was that he hopes Americans will take the information they need from scientists rather than politicians. Everyone must work together to convey the message about the role of vaccines, Collins said.
The nation must turn the tide on all the misinformation that’s circulating about the vaccines, Collins said, adding that it would be heart-breaking to have a COVID-19 vaccine developed and then have people refuse to use it.
Adams went a step further, calling on the HELP members themselves to use their “bully pulpits to shout” that vaccines are safe and effective. “People must stop attacking the process. … That’s instilling hesitancy and it’s hurting us,” he said, not just with COVID-19 but with other preventable diseases as well.
Cost of hesitating
Measles is a case in point. In 2000, the U.S. was measles free. But since then, people have forgotten that measles and other so-called childhood diseases can be life-threatening, Collins said, and many stopped getting their children immunized. As a result, more than 1,000 cases of measles were reported in the U.S. last year.
Because of vaccine hesitancy, 42,000 children are at risk of dying each year due to infectious diseases that could have been prevented. Collins said the misinformation that has produced those numbers angers and frustrates him. To help get the point across, he said he sometimes wears a T-shirt that proclaims “Vaccines cause adults.”
In addition to vaccine hesitancy, the pandemic itself has slowed down immunization programs as people were leery of going to health care providers unless it was a necessity. As a result, many families skipped their children’s vaccines this year. In opening the hearing, HELP Chair Lamar Alexander (R-Tenn.) said childhood vaccines across the nation declined more than 40% from February to April as the pandemic took hold.
Acknowledging that decline, Adams said, “I’m incredibly concerned that … almost 5 million children are behind on their vaccinations because of COVID.”
While those vaccines should be brought up to date, according to Adams and Collins, it may be awhile before children will be able to get a COVID-19 vaccine, even if one is approved this year. To date, none of the six candidates entering, or in, trials has been tested in anyone younger than 18, although one may begin testing teens in the next month or so, Collins said.
Typically, a vaccine is first proved safe and effective in adults before being tested in the 12-to-18 age group, Adams said. Then they’re tested in younger children.
Given the expectancy of a surge in COVID-19 later this year, Collins and Adams also stressed the importance of everyone getting an influenza shot this year. Adams added that vaccines are the quickest and easiest way for minorities and at-risk populations to protect their health, saying vaccines will help achieve health equity and social justice.