By Brandi Greenberg, Vice President, Life Sciences and Ecosystem Research

Let's do this a third time.

Back in September, when the first coronavirus vaccine trials were still underway, I wrote an article called "A vaccine approval is coming. Get ready to ask these 8 questions." My goal was to pre-commit myself to a framework for evaluating FDA's decisions, to ensure that—when the time came—I could objectively consider whether a vaccine had truly been proven safe and effective.

Radio Advisory episode: Vaccinating the globe, the ultimate systemness challenge

In December, I used my "cognitive toolkit" to put both the Pfizer-BioNTech and Moderna vaccines to the test. Now, I turn my attention to Johnson & Johnson's (J&J) vaccine, which FDA is expected to authorize for emergency use later today. If authorized, it would be the first single dose vaccine available, significantly simplifying distribution, scheduling, and patient data tracking. It removes the logistical headache for providers and public health agencies, who currently need to make sure vaccine recipients return at the right time, and receive the right brand, for their second dose.  Further, governments can release all doses as soon as they receive them, rather than calculating how many doses they need to withhold in order to ensure patients receive full two-dose protection. It’s a remarkable development.

My 8 biggest questions, answered

Before we dive in, a disclaimer: I am not a clinician and don't have a medical background. But I've spent the last 20 years researching the health care industry with a particular focus on pharmaceutical companies—so I think I have a good grasp of the key issues at play.

1) Did the vaccine follow the traditional approval pathway, rather than being approved under an emergency use authorization (EUA) or other nontraditional path?

Technically not. FDA is expected to authorize the J&J vaccine under an EUA based on two months of safety data. According to Dorian Fink of FDA's clinical division of vaccines and related products applications, drugmakers must collect six months of safety data to apply for full approval.

But as I said with Pfizer's and Moderna's vaccine (which were similarly authorized based on two months of data), I don't consider this a cause for concern. FDA is making a reasonable choice to await more data before issuing a final approval, and in the meantime, the EUA process allows for a rigorous review of all available trial data, with an eye toward maximum benefit and minimal harm.

2) Was clinical trial data on the vaccine released to the public?

Mostly Yes. As with Pfizer and Moderna's vaccine, FDA published its lengthy analysis of J&J's clinical trial data—62 pages, in fact. FDA's Vaccines and Related Biological Products Advisory Committee is slated to meet today, February 26 to discuss the results, and that meeting will be livestreamed to the public. J&J also released an in-depth, 119 page briefing document providing full information on their clinical trial design, data, and analyses.

According to FDA, J&J conducted a double-blinded, placebo-controlled study of about 40,000 participants on three continents—half of whom received the single-dose vaccine, and half of whom received a placebo.

3) Does the available study data clearly show that the vaccine offers meaningful, measurable protection from Covid-19 – such as fewer people getting sick, fewer people getting severely ill from Covid-19, or fewer people transmitting the virus after exposure?

Yes. Based on results from the global trial, J&J's vaccine is 66.9% effective at preventing moderate to severe/critical Covid-19 14 days after the single-dose vaccine, and 66.1% effective 28 days after the dose. In the United States, the vaccine was 85.9% effective against severe forms of Covid-19. Yes, this effectiveness is lower than Pfizer's reported 95% effectiveness and Moderna's reported 94.5% effectiveness, but what’s most important here is that J&J’s vaccine provides strong protection against hospitalizations and deaths. Across all U.S., Brazilian, and South African sites, there were no hospitalizations or deaths starting 28 days after vaccination, among those who received the J&J vaccine.

Remarkably, the vaccine was 81.7% effective against severe forms of Covid-19 in South Africa—indicating that the vaccine may sufficiently protect patients against serious disease caused by the highly transmissible B.1.351 variant. The vaccine was also 87.6% effective against severe Covid-19 cases in Brazil, where another highly transmissible variant has gained hold. When comparing efficacy data among vaccine candidates, it’s important to remember that these more-transmissible variants were not in circulation when Pfizer and Moderna ran their trials last year. Currently, J&J has another study underway to determine whether a second dose or booster of the vaccine could further bolster protection against the virus strains currently in circulation worldwide.

In terms of reducing virus transmission, the vaccine did show preliminary evidence of slightly reducing asymptomatic cases, which could be linked to a decrease in viral shedding rates. But because the sample size was very low, we still don't know enough to say with certainty whether the J&J vaccine can meaningfully reduce transmission of Covid-19. The government, researchers, and providers will need to collect more data to better understand the impact of this vaccine on transmission.

4) Did the vaccine clear the 50% threshold for effectiveness that FDA previously announced as its approval requirement?

Yes. Johnson & Johnson’s vaccine, like Moderna's and Pfizer's, significantly cleared this threshold. Though the margin wasn’t as big, 66.1-66.9% efficacy overall is still great news. To restate a point made earlier: there were no Covid-19-related hospitalizations or fatalities among patients who had been vaccinated at least 28 days previously—and that's what matters most.

5) Did the vaccine meet that effectiveness threshold for members of all major U.S. demographic groups (by age, gender, race, etc.)?

Mostly yes. FDA's report broke down the trial data by age, gender, race, ethnicity, and more. Participants were 62.1% white, 17.2% Black or African American, 3.5% Asian, 8.3% American Indian or Alaska Native and 0.3% Native Hawaiian or other Pacific Islander. In addition, nearly 50% of the participants were Hispanic or Latino. According to the report, vaccine efficacy rates "among the subgroups are similar to the [vaccine efficacy] seen in the overall study population."

But there is one notable exception: Data indicated that the vaccine was less effective (42.3% overall) in participants 60+ years old who had underlying conditions or comorbidities, such as diabetes or heart disease. Yet FDA is uncertain about the strength of this data, noting that "the confidence intervals are wide, and the uncertainty of the point estimate is large." There were fewer participants and a lower incidence of Covid-19 cases in this group, and a greater proportion of these participants were unblinded since this population became eligible for other authorized vaccines during the trial. The takeaway: the lower efficacy rating for this subgroup could just "reflect imprecision associated with smaller numbers of cases." It doesn’t mean the vaccine isn’t safe for seniors with comorbidities, but it does mean I’ll be watching for more data as ongoing safety and effectiveness studies continue.

Finally, like the Pfizer and Moderna vaccines, the J&J vaccine was not tested in children under the age of 18 or pregnant women, so we simply don't have data on its safety and effectiveness in these populations. Of note: Pfizer and Moderna have launched trials for kids and teens, and both Pfizer and Johnson & Johnson plan to move forward with clinical trials involving pregnant women.

6) Is there a robust plan to follow up with participants to determine how long protection will last? Do early signs indicate that immunity will be durable over time?

Yes. So far, there's no sign that immunity is fading, but because some patients received their last injection only a few months ago, it's too soon to say for sure.

According to the FDA report, J&J’s trial protocol requires volunteers to get a blood test 71 days post-vaccination, which might provide some insights into the vaccine's durability. Also, as I mentioned, J&J will continue to follow-up with participants and will allow all trial participants who received a placebo to receive the vaccine. They will encourage participants who crossover from placebo to remain in the study for up to 2 years after vaccination so J&J can collect data on "efficacy/effectiveness, safety, and immunogenicity."

7) Does trial data clearly show that the vaccine's benefits outweigh any safety concerns? Is there a plan to monitor safety once the vaccine is given to a much broader group of people?

Yes. Common side effects included injection site pain, headache, and fatigue, but side effects were generally mild to moderate, resolving within 1-2 days, with 1% to 2% reported as severe. On average, seniors reported fewer and milder side effects than those under 60 years of age. Ultimately, FDA said the vaccine has a "favorable safety profile" with "no specific safety concerns identified that would preclude issuance of an EUA."

J&J's trial also included a mechanism for tracking more serious side effects potentially related to the vaccine. Of note, vaccine recipients reported slightly higher numbers of non-fatal thromboembolic events and tinnitus than those who received the placebo, but the numbers were so small (15 vs. 10 for blood clots, 6 vs. 0 for tinnitus), that FDA concluded "data at this time are insufficient to determine a causal relationship between these events and the vaccine."

As I previously mentioned, J&J also will conduct long-term follow-up of participants in the ongoing clinical trials to monitor safety. They also plan to do active surveillance studies on vaccine safety and efficacy using health insurance claims and electronic health records.

One other thing in J&J’s favor here, at least when it comes to perceptions of safety that can increase vaccine uptake: their product is an adenovirus-based vaccine, a well-established vaccine platform based on decades of research. Their Ebola vaccine, already approved and in use, relies on this same vaccine technology. For patients who may be hesitant to take Pfizer’s or Moderna’s mRNA vaccines simply because the mRNA platform is so new (regardless of the stellar safety profiles to date), J&J’s more established adenovirus platform may be more palatable. And since every shot in every arm gets us one step closer to herd immunity, I’m thrilled that we will now likely have a second type of vaccine available for consumers.

8) Have any participants in the approval process criticized the decision or the process itself? Have outside public health experts, especially those who previously served as senior-level officials at CDC, NIH, or FDA, criticized the approval?

No. In fact, most public health experts have praised the vaccine's effect on reducing severe or fatal cases of Covid-19. "With a J&J vaccine, we'll be able to accelerate the vaccine rollout for our country and the world," Dan Barouch, a virologist at Beth Israel Deaconess Medical Center, said.

One more question to consider

As I’m now fortunate enough to have been vaccinated, it doesn’t seem right to ask if I’d take the J&J vaccine, as I asked myself with Pfizer’s and Moderna’s entrants. But if you asked me if I’d encourage my sister or my best friend to get the J&J vaccine, my answer would be a resounding "yes."

When I look beyond individual choices, what really excites me is the potential for J&J’s vaccine to dramatically expand vaccine access and uptake worldwide. J&J reported that nearly four million doses will be ready to ship in the United States when the vaccine is authorized for use. White House officials told governors on Tuesday that about 2 million doses of J&J's vaccine should be available next week, with smaller amounts shipping to states in the following two weeks. It might take some time for additional manufacturing and distribution to ramp up, but J&J has committed to deliver 100 million doses in the U.S. by June (with millions of doses also going to other countries), and they expect to deliver on their commitment.

This is particularly important because J&J’s vaccine does not require the ultra-cold storage of mRNA vaccines. It’s transported and stored at normal refrigerator temperatures. When coupled with the single-shot dosing, this makes J&J’s vaccine a great option for expanding access to harder-to-reach communities, and it may ease transportation and care coordination burdens for patients who live far away from medical facilities (esp. in developing countries). Thus, it has the potential to make a significant impact in the global effort to improve equitable access to Covid-19 vaccines.