COVID-19 Shutdown Exit Strategy?

[gerntz]

I give up. "Deaths" and "hospitalizations" seem to be more reliable than "cases" or "testing." but what could anyone conclude from this? Deaths undoubtedly lag hospitalizations, but how they could run counter to one another for weeks is hard to explain. Effective treatments haven't been found that I heard about. Guess I need to wait and watch.

Not that anyone here is trying to, but it would be easy to make a convincing case for improving or deteriorating progress for the state simply by choosing charts that agree with your established views. Some/many (news) sources are actively doing so...

Right or wrong, I'd explain it as hospitals are now better prepared to admit less-sick patients than they were 4-6 weeks ago, and so they do.

 

[Leo1277]

Right or wrong, I'd explain it as hospitals are now better prepared to admit less-sick patients than they were 4-6 weeks ago, and so they do.

While they may also be better prepared now, the downward trend in the hospital death rate simply corresponds to the downward trend in the hospitalizations 2-3 weeks earlier. Any upward trend in the death rates corresponding to the upward trend in hospitalizations that started about two weeks ago hasn't arrived yet. For the full gory details, you may want to read my earlier post.

About hospitals admitting patients, the fact that there are more hospitalizations now than two weeks ago means there were significant capacities two weeks ago; and for financial reasons, hospitals aren't eager to turn down patients.

 

[Leo1277]

To follow up, I have modified my spreadsheet to compute and track the ratio of new cases today to new cases one week ago, both on a 7-day rolling average. If that number goes above 1.0, it means cases are growing. I went back through the data to track hospitalizations the same way. Since the first phase of reopening on May 20, we have continued to reduce our hospitalized population at the rate of approximately 25% per week.

Great! Would you perhaps be able to share that spreadsheet for others to use? And related to that, some colleagues keep raving about the fact that Excel can now pull in (I guess they say "scrape") just about anything that can be found on a webpage you supply to Excel with specs how to find what you want. I am wondering if one could even use something like this to automate your procedure.

 

[Midpack]

While they may also be better prepared now, the downward trend in the hospital death rate simply corresponds to the downward trend in the hospitalizations 2-3 weeks earlier. Any upward trend in the death rates corresponding to the upward trend in hospitalizations that started about two weeks ago hasn't arrived yet. For the full gory details, you may want to read my earlier post.

About hospitals admitting patients, the fact that there are more hospitalizations now than two weeks ago means there were significant capacities two weeks ago; and for financial reasons, hospitals aren't eager to turn down patients.

That’s what I’m afraid of, and why I suggested I need to wait and see. The declining rate of deaths seems encouraging but maybe hospitalizations is telling us to brace for increasing deaths again. Maybe as others have said, despite no formal treatment/therapy options, maybe health care folks are learning how to help anyway - that would be great.

And it also points to being careful about drawing conclusions based on one trend...

 

[Leo1277]

That’s what I’m afraid of, and why I suggested I need to wait and see. The declining rate of deaths seems encouraging but maybe hospitalizations is telling us to brace for increasing deaths again. Maybe as others have said, despite no formal treatment/therapy options, maybe health care folks are learning how to help anyway - that would be great.

And it also points to being careful about drawing conclusions based on one trend...

Yep, we have to be very careful with any conclusions, and always know what we don't know and not fool ourselves. So far the pattern of hospitalization numbers changing from downward to upward prettily fits with the phase 1 open (almost too prettily), and a good test for this hypothesis will be when we look at death rates over the next few weeks. Since you are monitoring these data, please keep us posted about further developments.

 

[harllee]

Remdesivir, the antiviral that reduces hospital stays by around 4 days and consequently reduces deaths has been distributed to the largest hospitals in North Carolina. I am hoping that that drug will help reduce deaths as this second wave hits.

 

[Leo1277]

Remdesivir, the antiviral that reduces hospital stays by around 4 days and consequently reduces deaths has been distributed to the largest hospitals in North Carolina. I am hoping that that drug will help reduce deaths as this second wave hits.

Good to hear that they are starting to roll it out more widely. However, in the clinical trials it has been shown to reduce length of disease, but it it has been shown that it does not have an influence on death rate. But every step helps; also if it's widely used, then following Midpack's model, it may be important to look at hospital admission rates, and not at the totals of folks hospitalized, as that later number may decrease with remdesivir.

 

[harllee]

Good to hear that they are starting to roll it out more widely. However, in the clinical trials it has been shown to reduce length of disease, but it it has been shown that it does not have an influence on death rate. But every step helps; also if it's widely used, then following Midpack's model, it may be important to look at hospital admission rates, and not at the totals of folks hospitalized, as that later number may decrease with remdesivir.

Dr Ralph Baric, who helped discover Remdevisir, is a Professor at UNC near where I live. He recently spoke on the local radio station and said that the reason that the study did not show that the death rate was reduced was because the trails were stopped early before that question could be answered. The reason the trials were stopped early was that it was decided that Remdevisir was successful in reducing hospital stays and they wanted to get it out to hospitals ASAP. Dr. Baric said it was his opinion that the drug does reduce deaths. Remdevisir has to be administered intravenously in the hospital so it is only given to patients who have been admitted to a hospital. So it will not reduce hospital admissions but could reduce the number of days in the hospital per patient and consequently the total number of patients in the hospital. And if Dr. Baric is correct it could reduce deaths. The biggest problem now is that there is only a limited amount of doses available --each patient must receive between 5-10 doses. So there will have to be rationing until production can be ramped up.

 

[Chuckanut]

Dr Ralph Baric, who helped discover Remdevisir, is a Professor at UNC near where I live. He recently spoke on the local radio station and said that the reason that the study did not show that the death rate was reduced was because the trails were stopped early before that question could be answered. The reason the trials were stopped early was that it was decided that Remdevisir was successful in reducing hospital stays and they wanted to get it out to hospitals ASAP. Dr. Baric said it was his opinion that the drug does reduce deaths. Remdevisir has to be administered intravenously in the hospital so it is only given to patients who have been admitted to a hospital. So it will not reduce hospital admissions but could reduce the number of days in the hospital per patient and consequently the total number of patients in the hospital. And if Dr. Baric is correct it could reduce deaths. The biggest problem now is that there is only a limited amount of doses available --each patient must receive between 5-10 doses. So there will have to be rationing until production can be ramped up.

+1

In his interview on The Peoples Pharmacy he stated his view that only a few more weeks of data were needed to justify a conclusion that the drug also saves lives. He was not happy that is was cut short, IIRC.

 

[aiken]

Dr Ralph Baric, who helped discover Remdevisir, is a Professor at UNC near where I live. He recently spoke on the local radio station and said that the reason that the study did not show that the death rate was reduced was because the trails were stopped early before that question could be answered. The reason the trials were stopped early was that it was decided that Remdevisir was successful in reducing hospital stays and they wanted to get it out to hospitals ASAP. Dr. Baric said it was his opinion that the drug does reduce deaths. Remdevisir has to be administered intravenously in the hospital so it is only given to patients who have been admitted to a hospital. So it will not reduce hospital admissions but could reduce the number of days in the hospital per patient and consequently the total number of patients in the hospital. And if Dr. Baric is correct it could reduce deaths. The biggest problem now is that there is only a limited amount of doses available --each patient must receive between 5-10 doses. So there will have to be rationing until production can be ramped up.

I hope he's right, but it's a stretch to say it will reduce deaths just because he says so. Whatever happened to doing the science?

 

[Gumby]

I hope he's right, but it's a stretch to say it will reduce deaths just because he says so. Whatever happened to doing the science?

Sounds like you've found yourself an encore career. We'll avidly await your results.

 

[GravitySucks]

Much of Upstate NY was expected to move to Phase 2 opening today - Professional service providers such as barbers, realtors, insurance brokers thought they were going back to work. Then around 8 o'clock last night the Governor said the data hasn't been reviewed by the international panel. I think he means the British analytic company he contracted but no one's quite sure. Long story short, they were not allowed to open and people are getting p*"*sed off.

 

[Leo1277]

Dr Ralph Baric, who helped discover Remdevisir, is a Professor at UNC near where I live. He recently spoke on the local radio station and said that the reason that the study did not show that the death rate was reduced was because the trails were stopped early before that question could be answered. The reason the trials were stopped early was that it was decided that Remdevisir was successful in reducing hospital stays and they wanted to get it out to hospitals ASAP. Dr. Baric said it was his opinion that the drug does reduce deaths. Remdevisir has to be administered intravenously in the hospital so it is only given to patients who have been admitted to a hospital. So it will not reduce hospital admissions but could reduce the number of days in the hospital per patient and consequently the total number of patients in the hospital. And if Dr. Baric is correct it could reduce deaths. The biggest problem now is that there is only a limited amount of doses available --each patient must receive between 5-10 doses. So there will have to be rationing until production can be ramped up.

Let's hope that in the long run, his optimism will be justified, we need every useful tool we can add to the arsenal. However, he is one of the inventors of the drug, and so he may be naturally a bit biased.

The officially published study that I know about was announced by the WHO a few weeks back. It concludes that there was not a statistically significant effect, but below statistical significance, remdesivir helped shorten the course of the disease for some patients with lighter symptoms. But it also mentions there was a higher number of adverse effects leading to discontinuation for remdesivir compared to placebo. But I recall hearing Fauci being more optimistic about intermediate results from some ongoing studies that aren't completed and published yet, and I am curious what they will show.

Here is the link https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext and the summary of results is given below. Let's hope we will find more and more ways that help against that nasty virus.

Findings
Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.

 

[harllee]

I hope he's right, but it's a stretch to say it will reduce deaths just because he says so. Whatever happened to doing the science?

Dr Baric is a well know scientist who has studied various coronaviruses for 30 years. The reason the study did not continue to see if deaths were reduced is that it was stopped because the drug was so successful in reducing days of hospitalization they wanted to immediately distribute the drug to hospitals. Wouldn't it be logical to say that deaths would be reduced it patients in the hospital started getting better and were discharged from the hospital 4 days early? I trust a highly respected scientist like Dr. Baric when he says that he thinks the drug will reduce deaths.

Personally if I get Covid-19 and have to go to the hospital I am going to try to go to a hospital that has a supply of Remdesivir.

 

[Leo1277]

Dr Baric is a well know scientist who has studied various coronaviruses for 30 years. The reason the study did not continue to see if deaths were reduced is that it was stopped because the drug was so successful in reducing days of hospitalization they wanted to immediately distribute the drug to hospitals. Wouldn't it be logical to say that deaths would be reduced it patients in the hospital started getting better and were discharged from the hospital 4 days early? I trust a highly respected scientist like Dr. Baric when he says that he thinks the drug will reduce deaths.

Personally if I get Covid-19 and have to go to the hospital I am going to try to go to a hospital that has a supply of Remdesivir.

Sounds great that UNC has such a distinguished faculty member. Do you have a link about this study? Note that according to the published Lancet study, positive effects for duration were mostly observed in patients with a lighter course of the disease, so it's not clear one could infer reduction in death rates. Also, the situation where a study is stopped usually happens when it becomes clear during the study that the regimen being tested somehow harms the participants. If here a clear benefit was visible, I suppose one could make an intermediate report about it that says it's sufficient to ship the drug to hospitals, but then continue as originally planned?

 

[Chuckanut]

IIRC, Dr. Baric said that Remdesiver also had to be given in the early stages of the disease. It’s really important to listen to the entire interview not just the parts that make the news.

 

[aiken]

Dr Baric is a well know scientist who has studied various coronaviruses for 30 years. The reason the study did not continue to see if deaths were reduced is that it was stopped because the drug was so successful in reducing days of hospitalization they wanted to immediately distribute the drug to hospitals. Wouldn't it be logical to say that deaths would be reduced it patients in the hospital started getting better and were discharged from the hospital 4 days early? I trust a highly respected scientist like Dr. Baric when he says that he thinks the drug will reduce deaths.

Personally if I get Covid-19 and have to go to the hospital I am going to try to go to a hospital that has a supply of Remdesivir.

Just a little too convenient for me. Why couldn't both be done...continue the study while simultaneously getting the logistics underway. In God we trust...all others bring data.

 

[harllee]

I don't have a link to the interview with Dr. Baric, it was on our local radio station and I don't see a link to it. I guess time will tell if Dr. Baric is correct about the reduced deaths but I am hopeful. In his interview he also talked about a second antiviral pill that is being developed in his lab--since it is in pill form it could be taken outside the hospital setting and could be taken as soon as someone was diagnosed. Dr. Baric said they were starting to do test on that pill and he hopes that it will be available by Fall.

 

[aiken]

I don't have a link to the interview with Dr. Baric, it was on our local radio station and I don't see a link to it. I guess time will tell if Dr. Baric is correct about the reduced deaths but I am hopeful. In his interview he also talked about a second antiviral pill that is being developed in his lab--since it is in pill form it could be taken outside the hospital setting and could be taken as soon as someone was diagnosed. Dr. Baric said they were starting to do test on that pill and he hopes that it will be available by Fall.

Yes, I agree he is a very impressive guy...I watched the whole video...believe it was on some program called the People's Pharmacy?



I was just a little deflated by the "Remdesivir for the Treatment of COVID-19-Preliminary Report" dated 5/22 in the NEJM. The final paragraph said "However, given the high mortality rate despite the use of Remdesivir, it is clear that treatment with an anti viral drug alone is not likely to be sufficient." Hopefully if it were given earlier in the disease progression, it would be more effective.

 

[Midpack]

Dr Baric is a well know scientist who has studied various coronaviruses for 30 years. The reason the study did not continue to see if deaths were reduced is that it was stopped because the drug was so successful in reducing days of hospitalization they wanted to immediately distribute the drug to hospitals. Wouldn't it be logical to say that deaths would be reduced it patients in the hospital started getting better and were discharged from the hospital 4 days early? I trust a highly respected scientist like Dr. Baric when he says that he thinks the drug will reduce deaths.

Personally if I get Covid-19 and have to go to the hospital I am going to try to go to a hospital that has a supply of Remdesivir.

Why couldn’t the study have continued at the same time it was administered to patients? I don’t know anything about Dr Baric, but I’d expect a lot more than “I think the drug will reduce deaths.” Lots of questions about the study and the control groups...

https://www.charlotteobserver.com/news/local/article242710841.html

https://dnyuz.com/2020/05/25/remdes...onavirus-miracle-cure-people-were-hoping-for/

The study was published in preliminary form in The New England Journal of Medicine on Friday, and it’ll require updating once the rest of the data from the 1,063 patients is gathered. But the conclusions section delivers the good news. “Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection,” the authors of the paper explained.

But that’s not all the study says. Later in the discussion section, it’s made clear that remdesivir alone isn’t enough. “These preliminary findings support the use of remdesivir for patients who are hospitalized with Covid-19 and require supplemental oxygen therapy,” the researchers write. “However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.”

As a reminder, researchers included in the study patients from the US and several other countries and divided them into two groups. 538 patients were assigned remdesivir and 521 were given a placebo, with doctors not knowing which medicine their patients received. The researchers found that those who received remdesivir recovered in an average of 11 days, 4 days sooner than the control group. Remdesivir did not have a statistically relevant effect on mortality, though. After 14 days, 7.1% of patients on remdesivir died, compared to 11.9% on placebo.

One other issue with the study might be the quality of the two groups. Slightly more placebo subjects started out in the more severe groups.

“I am not concluding from this that the treatment is not reducing time to recovery; it makes me less convinced that there is a mortality benefit when more placebo than intervention ended up in the highest risk group,” Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center director Peter Bach told Stat. He said a different remdesivir trial from Wuhan, China concluded that time to benefit was not significant, and it showed no mortality benefit. The doctor also criticized a separate study from remdesivir maker Gilead that compared two different durations of treatment without having a control group.

 

[harllee]

Midpack, the study you link says that 7.1% of patients on Remdesivir died while 11.9% on the placebo died, about a 40% reduction of deaths. The study did not find that significant but if I am the patient in the hospital I will take a 40% reduction since there is nothing else that helps at this time. On the interview I listened to on WCHL, my local radio station (which was a different interview than the People's Pharmacy interview, which I also listened to) Dr. Baric said he was disappointed and upset that the study did not continue on to make the determination about deaths so I don't know why it was actually stopped.

In any event about 1,000,000 doses have been distributed so far, with about 600,000 in the U.S.
8 large hospitals in North Carolina have received doses. Of course those doses will not last very long since each patient must receive 5-10 doses.

 

[6miths]

Midpack, the study you link says that 7.1% of patients on Remdesivir died while 11.9% on the placebo died, about a 40% reduction of deaths. The study did not find that significant but if I am the patient in the hospital I will take a 40% reduction since there is nothing else that helps at this time. On the interview I listened to on WCHL, my local radio station (which was a different interview than the People's Pharmacy interview, which I also listened to) Dr. Baric said he was disappointed and upset that the study did not continue on to make the determination about deaths so I don't know why it was actually stopped.

In any event about 1,000,000 doses have been distributed so far, with about 600,000 in the U.S.
8 large hospitals in North Carolina have received doses. Of course those doses will not last very long since each patient must receive 5-10 doses.

If it were 'true' that there was a 40% reduction in deaths then yes but 'not significant' means that there was a greater than 5% chance that the result of benefit was due to chance alone. And we know from many, many decades of experience that many small early studies that show a benefit are results that are due to chance. When larger studies are done, the 'benefit' disappears (and sometimes a 'harm' appears). There are many reasons for this phenomenon. One of the best slides I ever saw in an Evidence-Based Medicine talk was 'The bias of imminent men is still bias'. The students now like to say that we have moved from 'Imminence-Based Medicine' to 'Evidence-Based Medicine' but the move is far from complete and has been corrupted to some degree by Big Pharma and Big Medicine.

And bear in mind that most of the drugs being looked at are only potentially incremental in effect. Even if remdesivir proves to have a true beneficial effect on mortality you still would be much better off to not become infected at all. Are best hope is for an effective vaccine and that is still not a sure thing at all.

 

[Midpack]

Midpack, the study you link says that 7.1% of patients on Remdesivir died while 11.9% on the placebo died, about a 40% reduction of deaths. The study did not find that significant but if I am the patient in the hospital I will take a 40% reduction since there is nothing else that helps at this time. On the interview I listened to on WCHL, my local radio station (which was a different interview than the People's Pharmacy interview, which I also listened to) Dr. Baric said he was disappointed and upset that the study did not continue on to make the determination about deaths so I don't know why it was actually.

That’s grasping at straws, ignoring how statistics work, and picking out just what you want to hear. Did you also note the questions about how sample groups were composed? Other complete studies have come to different conclusions, what about them? You seem invested in the answer you want to believe. We’d all welcome any real good news re: therapies or vaccines, but we don’t have that yet. Some people were convinced Hydroxychloroquine was promising too based on sketchy data, Dr Baric’s credentials notwithstanding.

The article explained why the study was stopped. Did you read it?

 

[harllee]

That’s grasping at straws, ignoring how statistics work, and picking out just what you want to hear. Did you also note the questions about how sample groups were composed? Other complete studies have come to different conclusions, what about them? You seem invested in the answer you want to believe. We’d all welcome any real good news re: therapies or vaccines, but we don’t have that yet.

The article explained why the study was stopped. Did you read it?

Ok I give up-- I will just go back to my normal gloom and doom and being depressed. This drug and Dr Baric had given me some hope that if I or my DH with health problems or my 90 year old mom got the virus (even though we are doing everything we can to avoid to avoid it) and ended up in the hospital there would be some chance we could recover. Oh well.

 

[aiken]

Ok I give up-- I will just go back to my normal gloom and doom and being depressed. This drug and Dr Baric had given me some hope that if I or my DH with health problems or my 90 year old mom got the virus (even though we are doing everything we can to avoid to avoid it) and ended up in the hospital there would be some chance we could recover. Oh well.

I wouldn't give up hope...I feel the same way sometimes. We have the best minds in the world working on this problem, and I'd bet within a few months there will be a breakthrough that mitigates the worst outcomes. I've been watching the antibody therapy work that shows real potential...maybe more so than a vaccine.