Some of the Gilead Remdesivir Results from Recent Studies
Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19A Randomized Clinical Trial, JAMA, Christoph D. Spinner, MDRobert L. Gottlieb, MD, PhDGerard J. Criner, MD, August 21, 2020
This is a freebie so you should be able to get into this article and pickup on additional detail. Those who were treated early on had a better result from remdesivir than those who were treated later after contracting Covid. This was already know,.
Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group.
On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02).
The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.
Some Limitations: This study has several limitations. First, the original protocol was written when COVID-19 cases were largely confined to Asia and the clinical understanding of disease was limited to case series. This led to a change in the primary end point on the first day of study enrollment as it became clear that hospital discharge rates varied greatly across regions and the ordinal scale had become standard for interventional COVID-19 studies. Second, the study used an open-label design, which potentially led to biases in patient care and reporting of data. Third, because of the urgent circumstances in which the study was conducted, virologic outcomes such as effect of remdesivir on SARS-CoV-2 viral load were not assessed. Fourth, other laboratory parameters that may have aided in identifying additional predictors of outcomes were not routinely collected. Fifth, the ordinal scale used to evaluate outcomes was not ideal for detecting differences in patients with moderate COVID-19, especially for a clinical situation in which discharge decisions may be driven by factors other than clinical improvement.
This is BS.
if by “this is BS” you mean it’s mumbo-jumbo, run, then i’m ok with that, because it’s pretty much mumbo-jumbo to me…but if you mean there’s something in that article that’s a fabrication or falsehood, then you’d best clue me in, because my ability to pick apart that kind of study for potential inaccuracies is seriously limited…
What are you calling BS on?
Earlier studies showed remdesivir to be marginally better than standard of care, maybe knocking a day or two off the worst of the disease. It wasn’t a miracle cure, but like tamiflu, which has a similar effect, it could be useful.
Some things I found interesting were:
1) Standard of care included hydroxy/chloroquine for almost half the patients and azithromycin for a good number of others. Patients given remdesivir, were not given chlorquine or azithromycin. This means that chloroquine and azithromycin work about as well as remdesivir. (There was no mention of zinc which is one of the running gags over at In The Pipeline.)
2) They did an open label study, which often introduces placebo bias in favor of an experimental drug, because they couldn’t round up enough extra containers for a proper placebo. Talk about resource constraints.
3) There were one hundred and five hospitals involved in studying about 600 patients. This, like most drug studies, sounds like a logistical nightmare. How many people did they have just calling the clinicians and trying to track this thing?
3) I loved their discussion on hiring an outside randomization consultant. How many kids want to be randomization experts when they grow up? Some kids are naturals. (They almost certainly hired one of those specialized consulting companies to figure out how much remdesivir they’d need.)
4) They mention that a lot of patients were discharged at the end of their remdesivir dosing. The study even suggests that patients in the ten day arm might not have done as well because they were kept in the hospital longer.
5) To my naive eye, the day 11 recovery rate looks best for the ten day arm followed by the five day followed by standard of care. My limited exposure to statistics has taught me that trying to understand statistics with the naked eye is like trying to see X-rays, so I’ll have to take their, or their statistical analyst consultants’, word that the results weren’t statistically significant.
6) The same table has me asking why more patients were considered recovered than clinically improved. Surely recovering should be considered a clinical improvement, but I’m not a doctor, so ….
7) Just about everyone who didn’t die was much better after 28 days of treatment. That still leaves a lot (5-10%) of the patients still in crummy shape after four weeks, but at least they weren’t dead, at least not after 28 days.
I didn’t pick up a BS vibe. Just about every drug study I’ve read leaves me just about as mystified and amazed. It’s like those fractured fables where one is never quite sure what the moral is.
Kaleberg:
Just finished the PDF. About a decade ago, I received a LSS Black Belt which benefited me in manufacturing. Big take away was it only points in a direction which requires additional study of the initial findings. I am somewhat lax today in keeping up with it. On your second #3 that is a good question and thought. Stats are really not pursued enough today. I thrived on numbers.
On #1, Look up the recent 2020 nonrandom Henry Ford hospital study and subsequent open letter (2,541 patients). https://www.henryford.com/news/2020/08/hydroxychloroquine-an-open-letter
On #2, Unbelievable! Not enough vials.
On #3, Very true. Getting children interested in math can be difficult to do
On #5, I thought it to be the 5 day treatment as opposed to the 10 day treatment. However when they first started to use remdesivir, it was found to have a greater impact on Covid early-on in the treatment which I assume is what they were alluding to. I will reread it to gain a clearer understanding
On #6, Covid has not shown a propensity to just go away. It lingers in other forms such as weakened bodily organs. This may be what they are stating. Over at reddit, they had commentary by those having contracted Covid. Their ordeal dealt with months before it subsided. Better yes, dischargeable perhaps, but lingering ong afterwards.
I don’t understand why you call this “BS.”
Joel:
To see who is reading this. You are also one of the few here who give offer some thoughts on the topic.
@Run,
Thanks. I think BS is a bit strong. The authors make clear the caveats, which are many and limit the findings as a guide to action.
Joel:
It was meant to be strong to seek disagreement.
I am most of the way through the PDF (which I believe Kalesburg read and probably you) now. I find it disappointing as we are not much further ahead than before. And you are right on caveats findings being limited. However, people are viewing this as a cure and not as a treatment which has appeared to be more effective early on in the treatment of Covid. There will be great disappointment on their part. There is concern on pricing which I find interesting as it is relatively low in comparison to drugs such as Rituxan which has been found to work with me. I believe the med-cost is not overwhelmingly expensive; however (again), Gilead will benefit from the volume. Gilead has another and similar drug which requires less processing which supposedly acts in a similar manner. I am hoping they are moving this one along.