Author: Will Humble

In a normal clinical trial for a vaccine, a person in the vaccination group is given the vaccine while those in the placebo group get something like a saline injection. Both groups then go out to the community. Observations are made over time in both the vaccine and placebo groups to determine whether the vaccine protects people from infection.

There’s another kind of trial which speeds things up a lot called a “Challenge Trial”.  That’s when a person is vaccinated and then is later intentionally exposed to the virus to see whether they get sick.

There are obviously some ethical questions about challenge trials but they have some real advantages as well because they can speed up getting results by weeks or even months. You get cleaner data as well because you are sure about the exposure. So, in a public health emergency – when people are losing their lives every day- should we be using Challenge Trials to speed things up? After all, you know for sure that people are dying every day and that if you can speed up the trial, you’ll be able to save many lives by accelerating the trials.

Persons in Challenge Trials are volunteers. They are also done after  the Phase II trial has been completed so you have at least some information about the safety.

On the other hand, you may need to challenge persons that got the placebo (not the vaccine)…  posing clear ethical questions.  An alternative could be to challenge just the vaccine group (not the placebo group) with various doses of challenge virus and look to see whether there’s a dose-response. That might be a way around exposing the placebo group.

Anyway- take a look at this essay about Challenge Trials in Medscape this week.  Interesting short read.

Here’s a link to Dr. Gerald’s latest Epi report for Arizona. Below is his introductory paragraph. You can go to the full weekly report at this link.

For the week ending October 25th, 7221 new Covid-19 cases were diagnosed in Arizona (Figure 1). This represents a 19% increase from last week’s revised tally of 6064 cases. Reporting delays continue to be minimal.

Accordingly, last week’s tally of 5779 new cases was only upwardly revised by 5% (285 cases) this week. Some of this backfill was also attributable to moving this report earlier in the week. Case counts continue to increase among all age groups (Figure 2 following page). Rising case counts warrant reappraisal of government policies as well as individuals’ adherence with face masks, physical distancing, and hand hygiene practices. Current transmission levels are just shy of those observed during the first week of June when 8239 cases were diagnosed. A mere 3 weeks later, Arizona’s case count reached a peak of 27796 cases.

Given the possibility of exponential growth, current conditions could deteriorate rapidly.

CDC released new guidance strongly recommending face masks be worn by all passengers and personnel while on public transportation (including airplanes, ships, ferries, trains, subways, buses, taxis, and ride-shares) and at transportation hubs (such as airports, bus or ferry terminals, train stations, and seaports).

The FDA approved a remdesivir medication called “Veklury” to treat COVID-19 in people 12 years and older (and weighing over 88 lbs.).  The medicine is only approved for COVID-19 treatment if it’s administered in a hospital or other acute inpatient care facility.

This is the first medication that has been fully approved for the treatment of COVID-19. Many other medications have been given Emergency Use Authorization for use in patients with COVID-19 but this is the first med to be fully approved for treatment. The drug appears to help some patients recover more quickly but it hasn’t been shown to improve survival chances.

A clinical trial found that it accelerated recovery among patients that had advanced disease. It was a randomized, controlled trial involving 1063 patients.  The study found that patients who got remdesivir recovered 31% faster than the people that got the placebo (p<0.001). The median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for the placebo group.

Here’s one of my previous blog posts that walks you through how the FDA processes work when evaluating and approving medications. Here’s where you can read FDA’s press release on the remdesivir approval.

Was it a good decision?

The main drivers for managing COVID-19 risks in Arizona schools are the mitigation measures that are in place to prevent the spread of the disease in schools. The other important factor is the level of community spread within the district. Both are important factors for school governing boards to use as they make these important decisions.

Earlier this week the ADHS quietly changed the criteria that they recommend school districts use to make decisions about whether to use in-person, hybrid or virtual instruction. Arizona uses three different metrics for the benchmarks: percent positivity, cases per 100,000 and something called COVID-like illnesses reported by hospitals.

The first 2 metrics are solid benchmarks. Both percent positivity and cases per 100,000 are routinely reported across the public health system now- and both rely on firm diagnoses. Covid-like illness, on the other hand, is voluntarily and sporadically reported and largely subjective. It comes through a voluntary system called “Biosense”.

The guidance that was established a few months ago stated that “Schools should start preparing for virtual learning when one or more of the benchmarks are in the substantial spread category”. Under the guidance established this week, the Department now says that “district leaders to move from hybrid to virtual learning if all three benchmarks move to substantial for two weeks”.

The problem with that change from my perspective is that it puts decision-making emphasis on all three indicators even though only 2 of the indicators are solid ones (case rates and percent positivity). Covid-like illness is only a syndromic surveillance indicator that is subjective and sporadically reported. Putting Covid-like illness on par with the others and stating that all 3 indicators need to be in the ‘substantial’ range before going to virtual instruction puts more emphasis than is reasonable for that indicator.

Members of school governing boards may not understand that the Covid-like illness is a flimsy metric and may very well make decisions based on the assumption that it is a good indicator of community spread. It is not.

Take Graham County as an example right now. Both their cases per 100,000 and percent positivity are well within the substantial range and have been for 2 weeks… yet Covid-like illness is firmly in the ‘good’ range. This new guidance could give the impression to Graham County governing board officials that their decision to keep in-person rests on good evidence (the fact that Covid-like illness is still in the ‘good’ range) when in fact that indicator is unreliable.

Perhaps the decision to keep the guidance developed this week will be reviewed after additional scrutiny.