METHODS
We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.RESULTS
Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04).
This is good evidence that remdesivir is useful as a therapeutic. The study is a gold standard randomized clinical trial without the typical confounding seen in observational studies. It does not have selection effects and the statistics indicate a high confidence in at least recovery effects. Median recovery time is 26% (4/15) faster for people administered the drug than people who received placebo and regular care. Remdesivir does not have proven mortality effects at this time.
So what is its value?
I think remdesivir has two value propositions in the United States. In the current environment where hospitals are currently not overrun, it has real value in reducing hospital stays by 26% and reducing PPE, supportive medication and staff time demands to treat any one patient. This is valuable.
In an environment where a region’s hospitals are being overwhelmed, surging remdesiver into a region has both the baseline value and then an add-on value. A region with an overwhelmed hospital system will have a case fatality rate several times higher than the same region with hospital capacity to spare. The faster recovery time means beds clear faster and the staff that would be committed to helping two patients recover per month would be available to care for almost three patients per month. This would be a fast way to surge effective care capacity into a region that is the equivalent of deploying a hospital ship or an army field hospital with the attached train staff.
In that scenario, remdesivir will likely have indirect mortality effects. Shorter lengths of stay means the effective hospital throughput is higher which means the length of time that a region is in an overload scenario is shorter. Some individuals who would have been admitted to the hospital during a slam period without remdisivir will be admitted to the hospital during normal(ish) operations with far lower mortality risk due to the increased throughput.
Using this logic, remdesivir has both immediate resource replacement value and mortality prevention value in some scenarios. These two value streams can be modeled to be a fairly large number under some modeling assumptions. The value of the mortality prevention by minimizing periods of slam will be a function of modeling both COVID-19’s inherent response to seasonality, our social responses, our public health responses and the length of time to widespread, effective vaccine deployment. The less optimistic an analysis is about any of these parameters, holding all else equal, the more valuable remdesivir will be. But a fairly large number could be justified under standard cost effectiveness models depending on the underlying assumptions about disease spread and regional overload scenarios.
Nina
Nine years ago my husband was on a ventilator for 15 days after a flu led to pneumonia. On the 14th day they took me aside and told me to start thinking about giving him a tracheotomy, because 14 days was their rule of thumb for when throat and mouth damage usually started to get serious. I resisted, they took him off the next day and he breathed on his own.
Shorter time on the machine also pays off in a shorter post-illness recovery. Every day you are on there the muscles atrophy and there is a chance of permanent damage. I haven’t seen stories about it yet, but I wonder when we will start seeing the burnout among physical therapists. They have to be getting slammed.
BruceFromOhio
Presuming this is intravenous, why wouldn’t this be included as baseline treatment for all COVID-19 admissions? Unless this stuff is a jillion dollars a dose, just do it. Like Nina says, any way to reduce ventilator time is valuable for everyone involved.
WereBear
It makes me curious about other anti-viral therapies. There are broad-spectrum ones, though I don’t know how expensive those might be.
Cheryl from Maryland
@WereBear: yes, I’ve read several articles, which as a layman I can only guess their value and accuracy, suggesting there are other anti-virals which are thought to work as well or better than Remdesivir, but are cheaper and either off patent or close to it and don’t seem to be on their way to gold standard clinical trials. One, GS-441524, was developed by the same pharmaceutical company as Remdesivir. Why are they not bring tested? Greed is, of course, the first thing that springs to mind. https://www.statnews.com/2020/05/14/gilead-should-ditch-remdesivir-and-focus-on-its-simpler-safer-ancestor/
Cermet
Hopefully, the virus does not mutate and make this treatment less or not effective.
LightCastle
My recollection is that Gilead is well known for being aggressive on price. They aren’t going to sell a cheaper version if they can sell a more expensive one, and they aren’t going to let other things on the market if they can block them.
(Will be happy to find out I am misremembering this.)
Delk
Biktarvy, my current HIV drug costs $3496.99 a month. Throughout the 30 plus years I have been on just about every ‘miracle drug’ that came down the pipeline. Several made me sick. One in particular put me in the hospital for close to 2 incredibly painful months.
edited for typo
Benw
“This is great and all but it’s no bleach and sunshine.” – Dr. Trump
XD
waspuppet
@Benw: Oh no — I remember when Trump gave his first HYDROXYCHLOROQUINE IS THE CURE “press conference,” he briefly mentioned remdesivir too — he couldn’t even pronounce it. But if it turns out to be effective, he’ll be I CALLED IT AND EVERYONE LAUGHED AT ME all the way through Election Day.
This entire campaign is going to be the equivalent of holding up an apple, telling people it’s an orange and seeing how many people will agree.
boatboy_srq
@Benw: Since there is solid science behind the remdesivir finding, it’s virtually guaranteed Lord Dampnut and his host of gleeful assassins will want nothing to do with it.
gene108
@Cheryl from Maryland:
I’ve been in a couple of clinical trials for new uses of drugs, and each one was sponsored by the pharmaceutical company that made the drug.
The doctors, and researchers wrote up the findings, but the money to actually have the drug for free to people on the trial, some of the labs to monitor effectiveness, etc. were all paid by the pharma company.
The Moar You Know
@BruceFromOhio: Problems:
Another Scott
Thanks for this.
A couple of questions:
Thanks again.
Cheers,
Scott.
Brit in Chicago
This study was on people who were already very sick. I’ve been wondering whether there are trials which involve giving the drug to people why they first show symptoms and test positive. I’ve poked around a little but don’t see any evidence of there being such trials, though you’d think it would be a no-brainer. Anyone know the story there?
Cheryl from Maryland
@gene108: Yes, you are correct; it was better once but as my husband’s career at the FDA revealed, it became worse starting with Bush I as there the agency relied more on fees and findings from the pharmaceutical companies. However, it needs to change.
Nicole
@Cheryl from Maryland: That was an interesting read. And you’re right that without a profit-motivation, there’s no real reason for a pharmaceutical to pay for the research.
I recently started Tamoxifen for prevention of breast cancer recurrence, and having made the mistake of reading some breast cancer support boards, I was really, really scared about the side effects (note to self: support boards are often like customer service- people only call in to complain). That said, women giving up on the endocrine therapies due to quality of life issues with the side effects while only part way through treatment is an ongoing issue with breast cancer. There was a study recently (very small) on lower-dosage Tamoxifen that looked promising, but it’s unlikely there will be a follow-up, because, as one article pointed out, Tamoxifen is so cheap that there’s no financial motivation to see if lower doses than the standard are equally as effective at preventing cancer but maybe with fewer side effects. There’s great value of human life motivation in trying to find treatments that women are more likely to see through (as it’s a 5-10 year course of medication), but as it’s not something the pharmaceuticals can make money on, it’s nowhere on their list of priorities.
JCJ
@The Moar You Know:
I presume you are referring to hydroxychloroquine and not remdesivir. My daughter is furious about the misappropriation of the medication she needs for lupus. Don’t know if true but she read that in Utah hydroxychloquine was being given away. Her prescription ranges from $600 to $800 for a three month supply.
Victor Matheson
@Another Scott: Yeah, I obviously can’t tell survival distributions based on what was posted, but despite the note in David’s write-up that Remdesivir does not have proven mortality effects at this time, the NEJM article notes that death rates fell from about 11.9% to 7.1% or roughly a 40% fall. And this fall was just barely outside the statistical 5% significance level. So really, there is also a really strong suggestion that it not only cuts hospital time but also significantly increases survival rates. In fact, if they did this study once more and got the same results, pooling the two sample sizes together would result in a statistically significant result at the 5% significance level “proving” its effectiveness at preventing death in a statistical sense as well.
Victor Matheson
One more thing that is useful here is that if you can cut ICU time effectively increase the amount of ICU space you have available. I mean, if you have 10 beds and the average patient uses a bed for 15 days, you can treat 20 total patients per month. (You have 10 beds x 30 days = 300 bed/days divided by 15 days/patient = 20 patients.)
If you can use this drug and the ICU time drops to 10 days you can now treat 30 patients per month (300 bed/days divided by 10 day/patient = 30 patients.)
That’s a 50% increase in ICU capacity without adding a single bed.
Another Scott
Relatedly, https://cepr.net/a-gilead-remdesivir-fix-the-ten-percent-solution/
As usual, Dean Baker makes too much sense.
Cheers,
Scott.
Hoodie
@Another Scott: Not sure Dean understands the IP law involved. The feds could have other companies make remdesivir for use by the government, but his proposed compensation scheme would not fly with the courts. The standard for damages for patent infringement by the US Government is a reasonable royalty, which would normally be based on some theoretical market price of the drug, not how much it costs to produce it.
randy khan
@Another Scott:
I can say without reservation that is not how it would work. When the government takes property (and a patent is property), it has to give you just compensation, and the courts think that just compensation is what the thing is worth. Successful drugs always are worth a lot of money.
Not that the analogy is perfect, but if you bought a house in 2010 and sold it today, in most places the appreciation would be way more than 10%, and you would be entitled to the full value, not just 10% more than you paid.
Anonymous At Work
@randy khan: Government takes possession of patent and gives Gilead the expected value minus the government’s input as a percentage. So, if Gilead put in 25% of the funding from bench-to-bedside, they get 25% of the value.
Anonymous At Work
@Brit in Chicago: As someone in that exact field, such trials are difficult without widespread and aggressive testing. You’d have trouble “recruiting” and most mild cases aren’t seen in hospitals. In fact, a mild case being put into a hospital or inpatient setting would be an INCREASE in risk due to infection and such, to the patient, much less to the staff.
Testing prophylaxis in this scenario isn’t in the cards.
Victor Matheson
@Another Scott: Well, in theory a lot of this is right, but to really compensate Gilead and every other company, we would need to also pay their research costs (plus 10%) on all of the R&D that didn’t lead to usable new drugs. Every drug company in the world goes out of business if we give them a 10% return on the blockbuster drugs and make them eat all of the costs on research that doesn’t lead anywhere.
Mel
@Victor Matheson: Additionally, 4 fewer days of time hospital time means 4 fewer days of potential exposure to hospital-acquired pathogens (MRSA, VRSS, pseudomonas, c. difficile, etc.).
Especially important if results of current trials support the use of immune modulating / immune suppressing biologic meds to lessen the cytokine storm and try to prevent further Covid-19 induced autoimmune kidney and lung damage. Moving stable recovering patients who are no longer infectious home sooner is a win just about every way you look at it, if those patients have a functional support network available during their convalescence. That’s a big “if”.
My sibling is “recovered” from a presumptive Covid-19 infection that caused loss of sense of smell, Covid vascular lesions, then cough, sore throat and headache, then three weeks worth of high fever, severe pneumonia and respiratory distress, and the led to a secondary bacterial pneumonia. He is infection free, but 3 months out is still weak, debilitated, and struggling with residual autoimmune inflammation in his lungs. Walking to the mailbox exhausts him, and he’s an outdoorsy athletic person who runs, camps, bicycles, and canoes. This stuff is ferocious.
I worry that the failures in how our system deals with chronic illness and with short-term and long-term disability will cause even more damage to survivors.
LongHairedWeirdo
Fauci also seemed to give the impression that “now that we have *a* treatment, we’re likely to find others.” True? Not true? It seems reasonable, but unlike morons and Republicans, “I like it, and it seems reasonable” is reason to be *skeptical*. If you *want* it to be true, you bloody well have to have the null hypothesis ripped from your gripping hands by evidence. Otherwise, you might try to tease out a good result from a null.
Most importantly, we’ll *never* have to test double blind, placebo controlled for similar treatments in the future; we have a baseline and we can test versus *that*. That means no one else will be forced into a random no-treatment group.
Alas, as I understand it, remdesivir is only in IV form, and they’re giving it over days – it’s not a useful treat-at-home remedy, but, as already mentioned, by shortening time to recovery, it essentially expands hospital resources – something likely very important in the coming months.
Another Scott
@Victor Matheson: This (and others mentioned above) is a legitimate criticism of Dean’s back-of-the-envelope blog-post description. But he does understand the nuances and the ramifications. He’s written a free book about this (and other things) – Rigged.
Dean’s underlying thesis is that we have the economy we do because people set it up this way. Patents are in the Constitution because they were put there, not because they are some law of nature. The patent and trademark system could be (and has been) adjusted over time to change the incentives. (Will Disney ever lose the trademark on Mickey Mouse??!) We can and should change the incentives because they’re not working as they should.
E.g. Patents are driving up drug prices:
When was the last time someone tried to corner the market on polio vaccines…? ;-)
Cheers,
Scott.
What Have the Romans Ever Done for Us?
I asked about another drug in the same class as remdesivir in a thread last week…trade name is Avigan and generic is favipiravir. It has been lightly covered if at all in the US media but several countries (including the US) have ongoing clinical trials. The Chinese have stated that they think it is efficacious and are using it. It was approved for use against flu strains that don’t respond to other treatments in Japan in 2015.
The one trial I have seen (out of China) seems to show efficacy on par with remdesivir – it shortens the course of the infection by around 4 days. I only ask about this drug because it is available in an oral dose (as far as I know remdesivir is only available intravenously) and hence could be administered at home earlier in the infection before people get sick enough that they wind up in the hospital – thus potentially reducing the number of hospitalizations significantly. Also, the fact that Japan approved it a half decade ago seems like reasonable evidence that it has been vetted for safety. I’m wondering if anyone with health science expertise here has reviewed the studies of this drug and whether this drug shows promise.
burnspbesq
@Another Scott:
Except that Mr. Baker’s simple and obvious solution is blatantly unconstitutional.
Y’see, Dean, there’s this thing in the Fifth Amendment called the Takings Clause. If you want the patent, you have to pay fair market value for it, and the takeaway from a century of estate and gift tax valuation cases is that in litigation, the private party ALWAYS has better and more convincing expert witnesses.
WhatsMyNym
@What Have the Romans Ever Done for Us?:
The Times Of India is already on it.
Another Scott
@WhatsMyNym:
On the other hand, KyodoNews from May 26:
It doesn’t look like there’s a magic bullet for COVID-19 coming soon.
Cheers,
Scott.
LongHairedWeirdo
@Another Scott: It’s true that patents are driving up prices, but the secondary bit is, drug companies don’t want to produce drugs to help humanity; they want another Viagra or Lipitor. When you hear about how much money drug companies spend on research, remember, what they’re saying is “we didn’t just wanted a drug that worked; we wanted a patent on the full drug, and to reap *all* profits.”
That doesn’t mean drug companies are villains; GM doesn’t open source some of its cars, to save on costs, but cut into profits; drug companies are no different.
What it does seem to suggest, though, is that there’s likely lots of slack in drug research capabilities. If the US funded more general research, possibly with paybacks for use of certain research, we might learn a lot more, because there *are* eager scientists who’d love to find a new antibiotic, anti-malarial, anti-viral, etc., but won’t ever get hired by a drug company to research those relatively low margin drugs.
Heck, if that works out, let two companies bid for the license to sell the drug as if it were patented. That way, there’s a minimum of two companies competing for market share, which will lead to lower prices. (NB: this assumes the drug is profitable to manufacture and market – if it’s *not*, let it go straight to generic. Someone will figure out how to make it, with pennies of profit per dose; or,if it’s important (like an anti-malarial), even *that* can be subsidized.)
Another Scott
@LongHairedWeirdo:
Good points, but one minor quibble.
There are federal rules about automobiles – they have to satisfy safety and emissions requirements (for 10 years in many cases), parts have to be available for some extended period of time, they cannot void warranties for repairs made by non-dealers or prevent non-dealers from having access to parts, etc.
Similarly, we don’t have to have the drug market, and drug R&D, that we do. There are other ways of satisfying the human need for medication without having giant corporations collect monopoly rents.
Will it happen soon? Dunno. But it will happen sooner if we elect Democrats.
Eyes on the prizes.
Cheers,
Scott.
WhatsMyNym
@Another Scott: You left out a bit…
Carlo
There’s a third value of remdesvir, and of any effective anti-viral treatment: by reducing tissue viral load, and reducing the duration of the infective phase, it reduces infectivity, and hence the basic reproduction number (R0) of the epidemic. Widespread deployment can therefore help abate the epidemic.