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TLDRUpFront: Bamlanivimab is not the game-changer drug hoped for. Complexities and ethical questions in administration, distribution, and prescription remain. Still struggling with a drug that works is better than having no drugs that work at all.
My name is Therapeutic Rock!
FullContextInTheBack: So, lets get into it. I expect we will have to deal with a surly poltergeist or three by the end of this as we’ve said his name three times… but that’s just a risk we’re all going to have to face together.
Bamlanivimab is a monoclonal antibody that targets SARS-COV-2, the virus that causes COVID-19. Essentially, that means that it is the same thing – or very close to the same thing – your body already makes to fight the virus, once your immune system gets fully engaged in the fight. Thus, giving you an injection of this is essentially a kick-start to your immune system. That can be of major assistance in those people whose immune systems have trouble getting fully engaged – that is, older people, immunocompromised people, people with diabetes, sickle cell disease, etc – or people who are at risk of having a severe case of COVID-19 due to other comorbid conditions. On the other hand, in patients whose immune systems are already fully – or even OVER – stimulated, adding more bullets to the proverbial battlefield can be quite detrimental. Thus, it needs to be used carefully.
Part 1: Terms and Conditions
That brings us to everyone’s favorite part of every EULA ever: “Terms & Conditions.” The T&C under which doctors are authorized to prescribe bamlanivimab are –
- A person over the age of 11 who tests positive for SARS-COV-2 and weighs at least 40 kg (88 lbs), and
- Who is currently experiencing a mild or moderate case of COVID-19, and –
- Who is within 10 days (or 3 days; we’ll get to that) of symptom onset
- Who has a high risk of progressing to severe COVID-19 and/or requiring hospitalization, meaning any ONE of the following:
- Has a BMI >= 35
- Has chronic kidney disease
- Has diabetes
- Has an immunosuppressive disease
- Is currently receiving immunosuppressive treatment
- Are >= 65 years old
- Are >= 55 years old AND
- Has cardiovascular disease, OR
- Has hypertension (high blood pressure)
- Has COPD or another chronic respiratory disease
- Are 12-17 years old AND
- Has a BMI in the 85th or higher percentile for their age, OR
- Has sickle cell disease
- Has congenital or acquired heart disease
- Has a neurodevelopmental disorders (eg. cerebral palsy)
- Has a medical-related technological dependence like a tracheostomy, gastrostomy, or is on a ventilator for reasons unrelated to SARS-COV-2 infection
- Has asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
… now, be honest with me: did you get through all that? Mmmhmm. You are starting to see the problem. And, that’s only part of the story.
In addition to all of the above points of complexity, bamlanivimab must be given in an infusion center, takes an hour to give via an IV, and patients must be watched for an hour after it is administered in order to be sure that they are not going into anaphylactic shock or having another life-threatening adverse reaction. That means that it usually takes about three hours to administer it in said infusion center.
There are two problems with that.
First, infusion centers are MOSTLY used by people who are receiving chemotherapy (or many therapies for autoimmune disorders like Crohn’s, lupus or multiple sclerosis). Those therapies are by and large immunosuppressive, or at least result in the person being immunocompromised. That means that they are full of exactly the type of people you DO NOT WANT to catch COVID-19, the exact sort of people who are defined as high-risk by the above-listed set of qualifications. Unlike hospitals, infusion centers often have an open floor plan, and that means that isolation of one patient from another is often very difficult. This obviously presents a major problem for those centers.
Second, infusion centers are not urgent care. They give people routine medical treatment, and so are very much run in a routine fashion. Patients come in every month at the same time, are booked weeks in advance, and every slot is booked and the place kept as full as possible during regular business hours to optimize every labor hour and dollar spent on overhead. Adding an entirely new pipeline of patients to that mix, especially people who need to receive complex infusions as soon as possible after they are prescribed, throws that model into chaos. Adding infectious risk into that mixture makes it even more volatile.
What are we getting for all of that complexity? That is to say, what are the proven benefits of boomshakalakamab? Well, that bring us to…
Part 2: Bamlanivimab’s Benefits
Stock-photos of happy workers may take awhile to catch up with COVID19.
The best description of the study I could find (the full results have not yet been posted publicly, but because the trial is part of the FDA’s larger efforts to bring therapeutics to market as fast as possible they used preliminary, unpublished data to support the EUA) is:
~100 patients each were given a placebo, a low dose of bamlanivimab, and a high dose of bambalanivimab.
* After 11 days, the patients who received a low dose of beetlejuicebeetlejuicebeetlejuice had about a 3.4 times lower viral load than the patients who received a placebo.
* After 28 days, 1.6% of patients were hospitalized in the low and high dose bamlanivimab group lumped together, while 6.3% of patients in the placebo group were.
* If only considering those members of the study defined to be high risk (see above criteria) then those numbers change to 3% versus 10%.
Now, I want to be clear that that’s not nothing… but it is also not game-changing. It helps, but it does not mean the fight is over. It can only be given to a subset of patients, and in those patients it is of fairly modest benefit, and the data used to support that assertion has not been published nor fully vetted by the normal scientific process yet.
Why did it get so swiftly approved? The approval process is sometimes a bit of a black box, so I can’t really answer that. All I can say is that NIAID, NIH, CDC and the FDA are throwing every resource they can right now at swiftly developing therapeutics for COVID-19, in the hopes that with more tools to fight the pandemic we will reduce the mortality from the already-ongoing winter surge in cases. Perhaps that drove them to approve it more swiftly, and perhaps something else did. I can’t possibly say. In times like this, ethical choices get awfully murky, as needs start to pile up and drive people to do something about a pressing problem rather than sitting on their hands and waiting for a slow, regular – albeit authoritative – process to complete. That brings us to…
Part 3: Ethical Considerations
I have one final concern about the distribution and use of this therapy, though I am somewhat hesitant to bring this up because I do my best to keep politics away from the things I talk about.
Yeah, we’re going there. We kinda have to.1
I want to direct your attention to three pictures for a moment. The first picture is a graphical representation of the cases that each of the 50 states has reported in the last 7 days (I downloaded the actual numbers).
This map also doubles as 538’s Election Forecast.
The next is one of several pages (full link from phe dot gov in the ‘Sources” at bottom) showing how many vials of bamlanivimab was sent to each of those jurisdictions on Week 1 (09 Nov- 17 Nov) and Week 2 (18 Nov to 23 Nov).
The third picture is a graph I generated which shows the difference between the percentage of the total cases that was seen in every jurisdiction and the percentage of vials of bamlanivimab sent to hospitals in each of those jurisdictions.
Let me explain why I went about it in that way, before we dig into it further.
First, I found the strongest correlation that I could that explained how HHS allocated the various vials of bamlanivimab to the places it did. The strongest correlation (at r = 0.96044) was seen by comparing the percentage of the vials that were sent to a given location and the percentage of total cases of COVID-19 that were reported from that location in the last 7 days. That is a relevant public health metric to use, so I dug into it more to see which states represented a deviation from that correlation, and how. In order to do that, I subtracted the percentage of cases reported from the percentage of vials sent, and looked for the places with the largest difference. That is what the graph shows.
If a place has a positive value, then that means that they got more % of the bamlanivimab sent around the country than the % of cases that they reported out of the national total. Notably, there are some differences in which places are listed in either dataset (one set from the CDC’s COVID dashboard, the other from HHS’s PHE dot gov), and there are some places I was not able to list and some correlations I was not able to examine because of limitations in the various datasets.
All of that said, here are the things I found to be of note:
The states that received an outsized share of bamlanivimab (+0.5% or more) were:
Florida, Georgia, Illinois, Kentucky, Missouri, New York, Texas, and Wisconsin
The states that received an undersized share of bamlanivimab (-0.5% or more) were:
California, Minnesota, and Pennsylvania
(ignore New York City; that’s a data artifact, not a genuine result)
In addition to that, of ~120,000 vials of bamlanivimab sent around the country in the two-week period described on PHE, there were a few non-state jurisdictions that jumped out at me:
- The Bureau of Prisons received 100
- The Department of Defense received 300
- The Indian Health Service received 300
- The Department of Veteran’s Affairs received 300
Now, all of the above-noted cautionary statements and considerations borne in mind… that might not be a big thing, practically speaking. It may be that the IHS, DOD, BOP, and VA do not run enough infusion centers or have a high enough patient population to even benefit much from that many doses, and it may be that their EHR (Electronic Health Records) infrastructure is not agile enough to be able to direct this care to the people who need it. It may be that the states with a smaller share asked for less for whatever reason, or that the decision was made on factors not included in my analysis. It may also be true that even if prescribed to the whole population of at-need people in the last four groups, the total number of people who benefit from it might at most be 50 or 60 people. All of those factors are a relevant considerations.
However, it is worth thinking about the ethics of distribution because many other hospitals are gripping with just this sort of ethical question in a variety of ways. Bamlanivimab is a limited resource, so some places are using a blinded, randomized lottery to determine who receives the treatment. For others, a weighting system that takes into account its benefit relative to multiple comorbid conditions is the answer. For still others, it’s both. And, in the members of the last group the “secret sauce” algorithms – how much is COPD “worth” in the weighting? Obesity? Diabetes? >65 years of age? Immunocomprised status? – vary quite a bit. Those are being designed by medical ethics boards, hospitial review boards and sometimes by individual doctors in charge of medical records systems at a frenzied pace.
So, why were so few vials sent to some places, relative to their population? What drove the decision to send larger numbers of vials to various different places? It might be that it was simply an artifact of the data, owing to the fact that my “7 day” window was different than the window that HHS used and that had I used the same data the correlation would be perfectly 1-to-1. It may be because they used a composite calculation that took more than one factor into account. It might not. That approval process, though, is an ethical nightmare… and doubly so for it to be happening in the middle of a national election, when undoubtedly many powerful people have an interest in sending vials full of what may well be life-saving medication (or at least may well be perceived to be life-saving medication) to the constituencies they serve. It also exists within a cultural narrative of advantage and disadvantage, a history of abuse and neglect of certain groups of people, and a political environment fraught with divisiveness and unconcern. Unfortunately, while I would very much like to divorce these considerations from the public health aspects of the pandemic… at the end of the day, if I did that I would be blinding myself (and you) to precisely the sorts of hard truths that we all need to face in times like this.
These are the hard, unpleasant, but unavoidable ethical truths we can’t help but face in the midst of a pandemic.
Part 4: Bringing it Home
At the end of the day, all other factors aside… this is a good thing. I don’t want my criticisms and worries and ethical concerns to make one think otherwise. We have another tool now that we can use to fight a deadly disease, and none of the above-considered factors neutralizes that fact. We should be thankful to the many doctors, nurses, study volunteers, medical technicians and other people whose work helped bring this therapy to market. We should celebrate this moment along with the vaccines now working their way to approval, as this may mean that soon we are turning a corner on this pandemic. That is a most excellent holiday gift to humanity.
But we also need to understand the limitations, the challenges, and the complexities. We need to know what to expect, and we need to know how this tool will be used. Knowing that will help us to calibrate our expectations, and understand this gift for what it is rather than lamenting what it isn’t. It’s not a silver bullet solution; we all still need to be careful, be smart, and take proper precautions. But, it is a step in the right direction.
Happy Thanksgiving, an early (or maybe not) happy holidays, and please stay safe out there.
1 Note: I really do hope for a robust discussion on this point, and I look forward to someone proving me wrong. If you have something to add to this that I’ve not considered or a critique of my method that could impugn my findings, please don’t hesitate to speak up.