https://anthraxvaccine.blogspot.com/202 ... covid.htmlFriday, November 27, 2020
A closer look at U.S. deaths due to COVID-19/ Johns Hopkins Newsletter-CENSORED
https://web.archive.org/web/20201126223 ... o-covid-19This article was removed from the JHU Newsletter site! But it can be found using the waybackmachine at the URL above!
The article answers a sticky question about US Covid deaths: are they deaths with Covid, or deaths because of Covid? The answer, which has been obfuscated all year by federal public health agencies, is that in 2020 deaths coded as being caused by heart disease, cancer, etc. are way down, while deaths coded as due to Covid almost exactly fill in the gap that would have been filled in by other conditions, in any other year.
A closer look at U.S. deaths due to COVID-19
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According to new data, the U.S. currently ranks first in total COVID-19 cases, new cases per day and deaths. Genevieve Briand, assistant program director of the Applied Economics master’s degree program at Hopkins, critically analyzed the effect of COVID-19 on U.S. deaths using data from the Centers for Disease Control and Prevention (CDC) in her webinar titled “COVID-19 Deaths: A Look at U.S. Data.”
From mid-March to mid-September, U.S. total deaths have reached 1.7 million, of which 200,000, or 12% of total deaths, are COVID-19-related. Instead of looking directly at COVID-19 deaths, Briand focused on total deaths per age group and per cause of death in the U.S. and used this information to shed light on the effects of COVID-19.
She explained that the significance of COVID-19 on U.S. deaths can be fully understood only through comparison to the number of total deaths in the United States.
After retrieving data on the CDC website, Briand compiled a graph representing percentages of total deaths per age category from early February to early September, which includes the period from before COVID-19 was detected in the U.S. to after infection rates soared.
Surprisingly, the deaths of older people stayed the same before and after COVID-19. Since COVID-19 mainly affects the elderly, experts expected an increase in the percentage of deaths in older age groups. However, this increase is not seen from the CDC data. In fact, the percentages of deaths among all age groups remain relatively the same.
“The reason we have a higher number of reported COVID-19 deaths among older individuals than younger individuals is simply because every day in the U.S. older individuals die in higher numbers than younger individuals,” Briand said.
Briand also noted that 50,000 to 70,000 deaths are seen both before and after COVID-19, indicating that this number of deaths was normal long before COVID-19 emerged. Therefore, according to Briand, not only has COVID-19 had no effect on the percentage of deaths of older people, but it has also not increased the total number of deaths.
These data analyses suggest that in contrast to most people’s assumptions, the number of deaths by COVID-19 is not alarming. In fact, it has relatively no effect on deaths in the United States.
This comes as a shock to many people. How is it that the data lie so far from our perception?
To answer that question, Briand shifted her focus to the deaths per causes ranging from 2014 to 2020. There is a sudden increase in deaths in 2020 due to COVID-19. This is no surprise because COVID-19 emerged in the U.S. in early 2020, and thus COVID-19-related deaths increased drastically afterward.
Analysis of deaths per cause in 2018 revealed that the pattern of seasonal increase in the total number of deaths is a result of the rise in deaths by all causes, with the top three being heart disease, respiratory diseases, influenza and pneumonia.
“This is true every year. Every year in the U.S. when we observe the seasonal ups and downs, we have an increase of deaths due to all causes,” Briand pointed out.
When Briand looked at the 2020 data during that seasonal period, COVID-19-related deaths exceeded deaths from heart diseases. This was highly unusual since heart disease has always prevailed as the leading cause of deaths. However, when taking a closer look at the death numbers, she noted something strange. As Briand compared the number of deaths per cause during that period in 2020 to 2018, she noticed that instead of the expected drastic increase across all causes, there was a significant decrease in deaths due to heart disease. Even more surprising, as seen in the graph below, this sudden decline in deaths is observed for all other causes.
COURTESY OF GENEVIEVE BRIAND
Graph depicts the number of deaths per cause during that period in 2020 to 2018.
This trend is completely contrary to the pattern observed in all previous years. Interestingly, as depicted in the table below, the total decrease in deaths by other causes almost exactly equals the increase in deaths by COVID-19. This suggests, according to Briand, that the COVID-19 death toll is misleading. Briand believes that deaths due to heart diseases, respiratory diseases, influenza and pneumonia may instead be recategorized as being due to COVID-19.
COURTESY OF GENEVIEVE BRIAND
Graph depicts the total decrease in deaths by various causes, including COVID-19.
The CDC classified all deaths that are related to COVID-19 simply as COVID-19 deaths. Even patients dying from other underlying diseases but are infected with COVID-19 count as COVID-19 deaths. This is likely the main explanation as to why COVID-19 deaths drastically increased while deaths by all other diseases experienced a significant decrease.
“All of this points to no evidence that COVID-19 created any excess deaths. Total death numbers are not above normal death numbers. We found no evidence to the contrary,” Briand concluded.
In an interview with The News-Letter, Briand addressed the question of whether COVID-19 deaths can be called misleading since the infection might have exacerbated and even led to deaths by other underlying diseases.
“If [the COVID-19 death toll] was not misleading at all, what we should have observed is an increased number of heart attacks and increased COVID-19 numbers. But a decreased number of heart attacks and all the other death causes doesn’t give us a choice but to point to some misclassification,” Briand replied.
In other words, the effect of COVID-19 on deaths in the U.S. is considered problematic only when it increases the total number of deaths or the true death burden by a significant amount in addition to the expected deaths by other causes. Since the crude number of total deaths by all causes before and after COVID-19 has stayed the same, one can hardly say, in Briand’s view, that COVID-19 deaths are concerning.
Briand also mentioned that more research and data are needed to truly decipher the effect of COVID-19 on deaths in the United States.
Throughout the talk, Briand constantly emphasized that although COVID-19 is a serious national and global problem, she also stressed that society should never lose focus of the bigger picture — death in general.
The death of a loved one, from COVID-19 or from other causes, is always tragic, Briand explained. Each life is equally important and we should be reminded that even during a global pandemic we should not forget about the tragic loss of lives from other causes.
According to Briand, the over-exaggeration of the COVID-19 death number may be due to the constant emphasis on COVID-19-related deaths and the habitual overlooking of deaths by other natural causes in society.
During an interview with The News-Letter after the event, Poorna Dharmasena, a master’s candidate in Applied Economics, expressed his opinion about Briand’s concluding remarks.
“At the end of the day, it’s still a deadly virus. And over-exaggeration or not, to a certain degree, is irrelevant,” Dharmasena said.
When asked whether the public should be informed about this exaggeration in death numbers, Dharmasena stated that people have a right to know the truth. However, COVID-19 should still continuously be treated as a deadly disease to safeguard the vulnerable population.
Posted by Meryl Nass, M.D. at 4:32 AM 0 comments
Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—let’s be cautious and first see the full data/ BMJ
https://blogs.bmj.com/bmj/2020/11/26/pe ... full-data/November 26, 2020
Only full transparency and rigorous scrutiny of the data will allow for informed decision making, argues Peter Doshi
In the United States, all eyes are on Pfizer and Moderna. The topline efficacy results from their experimental covid-19 vaccine trials are astounding at first glance. Pfizer says it recorded 170 covid-19 cases (in 44,000 volunteers), with a remarkable split: 162 in the placebo group versus 8 in the vaccine group. Meanwhile Moderna says 95 of 30,000 volunteers in its ongoing trial got covid-19: 90 on placebo versus 5 receiving the vaccine, leading both companies to claim around 95% efficacy.
Let’s put this in perspective. First, a relative risk reduction is being reported, not absolute risk reduction, which appears to be less than 1%. Second, these results refer to the trials’ primary endpoint of covid-19 of essentially any severity, and importantly not the vaccine’s ability to save lives, nor the ability to prevent infection, nor the efficacy in important subgroups (e.g. frail elderly). Those still remain unknown. Third, these results reflect a time point relatively soon after vaccination, and we know nothing about vaccine performance at 3, 6, or 12 months, so cannot compare these efficacy numbers against other vaccines like influenza vaccines (which are judged over a season). Fourth, children, adolescents, and immunocompromised individuals were largely excluded from the trials, so we still lack any data on these important populations.
I previously argued that the trials are studying the wrong endpoint, and for an urgent need to correct course and study more important endpoints like prevention of severe disease and transmission in high risk people. Yet, despite the existence of regulatory mechanisms for ensuring vaccine access while keeping the authorization bar high (which would allow placebo-controlled trials to continue long enough to answer the important question), it’s hard to avoid the impression that sponsors are claiming victory and wrapping up their trials (Pfizer has already sent trial participants a letter discussing “crossing over” from placebo to vaccine), and the FDA will now be under enormous pressure to rapidly authorize the vaccines.
But as conversation shifts to vaccine distribution, let’s not lose sight of the evidence. Independent scrutiny of the underlying trial data will increase trust and credibility of the results. There also might be important limitations to the trial findings we need to be aware of.
Most crucially, we need data-driven assurances that the studies were not inadvertently unblinded, by which I mean investigators or volunteers could make reasonable guesses as to which group they were in. Blinding is most important when measuring subjective endpoints like symptomatic covid-19, and differences in post-injection side-effects between vaccine and placebo might have allowed for educated guessing. Past placebo-controlled trials of influenza vaccine were not able to fully maintain blinding of vaccine status, and the recent “half dose” mishap in the Oxford covid-19 vaccine trial was apparently only noticed because of milder-than-expected side-effects. (And that is just one of many concerns with the Oxford trial.)
In contrast to a normal saline placebo, early phase trials suggested that systemic and local adverse events are common in those receiving vaccine. In one Pfizer trial, for example, more than half of the vaccinated participants experienced headache, muscle pain and chills—but the early phase trials were small, with large margins of error around the data. Few details from the large phase 3 studies have been released thus far. Moderna’s press release states that 9% experienced grade 3 myalgia and 10% grade 3 fatigue; Pfizer’s statement reported 3.8% experienced grade 3 fatigue and 2% grade 3 headache. Grade 3 adverse events are considered severe, defined as preventing daily activity. Mild and moderate severity reactions are bound to be far more common.
One way the trial’s raw data could facilitate an informed judgment as to whether any potential unblinding might have affected the results is by analyzing how often people with symptoms of covid-19 were referred for confirmatory SARS-CoV-2 testing. Without a referral for testing, a suspected covid-19 case could not become a confirmed covid-19 case, and thus is a crucial step in order to be counted as a primary event: lab-confirmed, symptomatic covid-19. Because some of the adverse reactions to the vaccine are themselves also symptoms of covid-19 (e.g. fever, muscle pain), one might expect a far larger proportion of people receiving vaccine to have been swabbed and tested for SARS-CoV-2 than those receiving placebo.
This assumes all people with symptoms would be tested, as one might expect would be the case. However the trial protocols for Moderna and Pfizer’s studies contain explicit language instructing investigators to use their clinical judgment to decide whether to refer people for testing. Moderna puts it this way:
“It is important to note that some of the symptoms of COVID-19 overlap with solicited systemic ARs that are expected after vaccination with mRNA-1273 (eg, myalgia, headache, fever, and chills). During the first 7 days after vaccination, when these solicited ARs are common, Investigators should use their clinical judgement to decide if an NP swab should be collected.”
This amounts to asking investigators to make guesses as to which intervention group patients were in. But when the disease and the vaccine side-effects overlap, how is a clinician to judge the cause without a test? And why were they asked, anyway?
Importantly, the instructions only refer to the first seven days following vaccination, leaving unclear what role clinician judgment could play in the key days afterward, when cases of covid-19 could begin counting towards the primary endpoint. (For Pfizer, 7 days after the 2nd dose. For Moderna, 14 days.)
In a proper trial, all cases of covid-19 should have been recorded, no matter which arm of the trial the case occurred in. (In epidemiology terms, there should be no ascertainment bias, or differential measurement error). It’s even become common sense in the Covid era: “test, test, test.” But if referrals for testing were not provided to all individuals with symptoms of covid-19—for example because an assumption was made that the symptoms were due to side-effects of the vaccine—cases could go uncounted.
Data on pain and fever reducing medicines also deserve scrutiny. Symptoms resulting from a SARS-CoV-2 infection (e.g. fever or body aches) can be suppressed by pain and fever reducing medicines. If people in the vaccine arm took such medicines prophylactically, more often, or for a longer duration of time than those in the placebo arm, this could have led to greater suppression of covid-19 symptoms following SARS-CoV-2 infection in the vaccine arm, translating into a reduced likelihood of being suspected for covid-19, reduced likelihood of testing, and therefore reduced likelihood of meeting the primary endpoint. But in such a scenario, the effect was driven by the medicines, not the vaccine.
Neither Moderna nor Pfizer have released any samples of written materials provided to patients, so it is unclear what, if any, instructions patients were given regarding the use of medicines to treat side effects following vaccination, but the informed consent form for Johnson and Johnson’s vaccine trial provides such a recommendation:
“Following administration of Ad26.COV2.S, fever, muscle aches and headache appear to be more common in younger adults and can be severe. For this reason, we recommend you take a fever reducer or pain reliever if symptoms appear after receiving the vaccination, or upon your study doctor’s recommendation.”
There may be much more complexity to the “95% effective” announcement than meets the eye—or perhaps not. Only full transparency and rigorous scrutiny of the data will allow for informed decision making. The data must be made public.
Peter Doshi, associate editor, The BMJ.
Competing interests: I have been pursuing the public release of vaccine trial protocols, and have co-signed open letters calling for independence and transparency in covid-19 vaccine related decision making.
Posted by Meryl Nass, M.D. at 4:05 AM 0 comments