Volume 76, no. 12 December 2020
EBM is proving to be eminence-based medicine, with a trail leading to piles of money for barely tested treatments and vaccines.
Regulatory agencies promise not to relax standards for approval. But was there ever any doubt about the outcome as more than 600 centers geared up to administer the Pfizer mRNA vaccine, with 2.9 million doses expected to ship immediately after emergency use authorization was granted, and 15 million by the end of the year? With the Moderna vaccine EUA, the supply will increase greatly (Wash Post 12/12/20, tinyurl.com/y3tv9xhv).
An AAPS member who monitored the 9-hour Dec 10 FDA advisory committee meeting felt that FDA administrators were actively managing and influencing the discussion and outcome of the “independent” panel. Concerns expressed by a number of committee members included: recommending vaccination of 16-18-year-olds though they were excluded from the trials and are at low risk; lack of data on the incidence of longer-term adverse events, possibly auto-immune; lack of follow-up data since the 2-months data was already a month old; and sparse evidence for the reduction of clinical COVID though antibodies were produced.
The committee voted 17-5 that “Based on the totality of scientific evidence available,…the benefits of the Pfizer-BioNTech COVID-19 vaccine outweigh its risks for use in individuals 16 years of age and older.” After the vote, the chairman abruptly adjourned the meeting without the previously promised second vote on whether to insert the words “to date” after “evidence.”
Pharmacies were advertising the future vaccine weeks before study results were known and before approval, in violation of multiple advertising laws. Information for the public on vaccine developments will be filtered worldwide by the “Trusted News Initiative.” U.S. participants include Facebook, Twitter, Google/YouTube, Financial Times, the Washington Post, and many others. Operational since March, TNI also censors anything that it considers “harmful misinformation” about coronavirus or that might “disrupt democracy” during an election (tinyurl.com/y2xxz43t).
The Arizona Medical Association asks members to make selfies while they are being vaccinated to contribute to a promotional campaign on social media (tinyurl.com/y7jd66v6).
In July 2020, Yale University designed a study to test the effect of various messages on people’s willingness to take a COVID-19 vaccine. The tested motivations included personal or economic freedom, anger, self interest, community interest, guilt, embarrassment, and “not bravery” (tinyurl.com/yxha3oj7).
The Harvard School of Public Health exhorts us to remind people on a DAILY basis of the significant risk they are putting themselves and their loved ones at if they don’t get the vaccine.
Just what kind of science does this represent? Psychology? Artificial intelligence methods of “shared analytics” (https://tinyurl.com/y4cstsns) to develop an Early Warning System like that of TNI to identify and counter “misinformation”?
The Royal Society of Medicine’s COVID episode 55 (tinyurl.com/ybj3tup3) featured social psychologist Clifford Stott discussing “Policing Health in a Pandemic.” The UK’s policing style is less likely to provoke riots than the more heavy-handed enforcement on the continent, he said. The goal is to get “normative” rather than “instrumental” compliance, from internalizing the goals rather than fearing punishment. This is part of the “building back better” (Great Reset, AAPS News, November 2020) agenda. Policing will be needed to enforce the still more radical transformation in life to fight “climate change,” he noted.
The COVID preoccupation seems to be everywhere, even in the discussion of nuclear explosions on Ready.gov. Be sure to bring two masks per person and hand sanitizer to the shelter, and maintain social distance (https://tinyurl.com/y6weo3nz).
As California and other states are imposing increasingly severe lockdowns, there is still no evidence of benefit, particularly not of benefit exceeding harm. In fact, Belarus may present the “dispositive natural experiment,” writes David Stockman (tinyurl.com/ycyxaggy). The country’s long-standing dictator, Aleksander Lukashenko, is a “COVID denier,” who has refused to impose a lockdown, close schools, or cancel mass events. After a purportedly rigged election, there have been massive protests for months. Yet the daily new case rate was 3.4 times higher in the U.S., where 80-90% wear masks, than in Belarus, where people rarely do (640 vs. 186 per million). The cumulative U.S. with-COVID death rate is more than six times higher (894 vs. 130 per million). It is 1,980/million in heavy-duty lockdown New Jersey. Of course there are other variables such as reporting measures and a scarcity of “killer care” homes in Belarus, but extensive international comparisons provide no evidence for Faucian restrictions.
How Much Evidence Do We Need for Early Treatment?
Film-maker Leo Klein asks this question in a compendium of brief video clips by physicians and researchers discussing ivermectin and hydroxychloroquine (https://tinyurl.com/y97v6umf).
In 40 ivermectin studies, 100% show positive effects, with 87% improvement when used early (p = .00052). For HCQ, the probability that an ineffective treatment would generate results as positive as in the 172 trials to date is <1/1015 (hcqmeta.com).
Pfizer Evidence to Date
The Pfizer vaccine trial involved 18,198 who received vaccine and 18,325 who received a saline placebo. Seven days after the second injection, the following were observed in the fully vaccinated vs. the unprotected group, respectively:
- Hospitalizations: 1 COVID + 2 COVID-suspected with infiltrates vs. 3 from COVID
- Deaths: 2 vs. 4 (none COVID-related)
- Lymphadenopathy (64 vs. 6)
- Bell palsy (4 vs. 0)
- Injection site reactions (2,748 vs. 396)
Excluded from the trial were the 16 million COVID-recovered and 160 million with COVID-like syndrome not tested/confirmed, those on COVID prophylaxis medications, immunocompromised patients, and many more. Excluded from vaccination now: only those with prior severe allergic reactions, pregnant women, and children under age 16.
The potential effect on fertility is not known. The spike proteins of SARS-CoV-2 also contain syncytin-homologous proteins, which are essential for the formation of the placenta in mammals such as humans. In response to an inquiry by 13News, a Pfizer spokesman at first said: “We are not commenting on this other than to say we encourage the public to seek information about the COVID-19 pandemic from trusted public health bodies and/or their…healthcare providers” (tinyurl.com/ydzcex8n).
Later, a spokesman stated: “There is no data to suggest that the Pfizer BioNTech vaccine candidate causes infertility: The shared sequence between the spike protein and syncetin-1 “is too short…to plausibly give rise to autoimmunity.” [But there’s no data to rule it out.] Pregnancy outcomes have been the same with and without intercurrent SARS-CoV-2 infection (ibid.).
Vaccine News Briefs
Why You Still Need a Mask. An intramuscular injection of vaccine might not elicit mucosal antibodies in the nose, while suppressing serious symptoms. Vaccinated persons could become “silent spreaders” (NYT 12/8/20, tinyurl.com/y247ce5c).
Prepare Patients for Severe Reactions. To prevent vaccine hesitancy, the public should be warned what to expect. “Fever, aches show vaccine works” (Science 11/27/20).
Minimizing Absenteeism. Medical facilities might schedule vaccination, especially the second dose, just before days off, and not vaccinate the entire staff at once.
FDA Probes Five Allergic Reactions. There have been severe allergic reactions in multiple states. The suspected culprit, PEG (polyethylene glycol) (tinyurl.com/y94lfqb2), is used to maintain the integrity of the lipid that protects the mRNA. More than 70% of the population may have anti-PEG antibodies.
“The business of journalists… is to twist the truth, to lie bluntly, to pervert, to revile, to kowtow at the feet of big business…. We are tools and servants of the rich men behind the scenes…. They pull the strings and we dance…. We are intellectual prostitutes…. If I were to allow honest opinions to be printed in one issue of my newspaper, I would be like Othello before 24 hours had elapsed—my occupation would be gone.
ACTION OF THE MONTH
If you offer early treatment for COVID-19 by protocol similar to the McCullough or Zelenko methods, please add your name to a list we are compiling to help patients at bit.ly/covidearlytx
Biderman Chart of Coercion: 1956 and 2020
More effective than physical force, methods used by Chinese and Korean Communist interrogators to break U.S. Air Force prisoners of war were described by social-science researcher Albert D. Biderman. These included: isolation, monopolization of perception, humiliation and degradation, exhaustion, threats, occasional indulgences, demonstrations of omnipotence, and forcing compliance with trivial demands. Compare with the COVID-19 control regime (https://tinyurl.com/y6u65vaw).
Senate Hears Evidence for Early Treatment
On Nov 19, the U.S. Senate Homeland Security and Governmental Affairs Committee, chaired by Sen. Ron Johnson (R-Wis.), heard testimony on the successful use of hydroxychloroquine (HCQ) in the early home treatment of COVID-19 by Peter McCullough, M.D.; George Fareed, M.D.; and Harvey Risch, M.D., Ph.D. (tinyurl.com/yc3kqqwy). Dr. McCullough’s algorithm, which explains the three phases of the illness, is featured in the free AAPS Guide to Home-Based COVID Treatment (https://tinyurl.com/yb2xt6rd).
The only Minority witness was Ashish Jha, M.D., M.P.H., dean of the Brown University School of Public Health, who asserted that the “high quality” studies of HCQ that met his academic standards had failed to provide convincing evidence for the efficacy of HCQ—when used too late.
The Minority boycotted the second hearing on Dec. 8, at which AAPS executive director Jane Orient, M.D., testified (https://tinyurl.com/yyqx7rsv). This focused primarily on the successful use of the anti-parasitic drug ivermectin as prophylaxis and in early and late treatment, by Jean-Jacques Rajter, M.D., and Pierre Kory, M.D. Armand Balboni, M.D., Ph.D., spoke of the need to develop hybrid trial methodology, not relying solely on randomized controlled trials during emergencies. Jayanta Bhattacharya, M.D., Ph.D., a coauthor of the Great Barrington Declaration (https://gbdeclaration.org/), spoke about the devastating harms of lockdowns and the importance of re-purposed drugs including dexamethasone. Video recordings and written testimony are available on the committee website.
In advance of the hearing, Dr. Jha circulated a letter condemning it for “raising doubts about the scientific process,” “attacking the credibility of public health experts,” “undermining trust in medical science,” and endorsing “unfounded therapies.” The 50 signatories include Christine Cassell, Joycelyn Elders, Monica Gandhi, Lawrence Gostin, Peter Hotez, Bernard Lo, Eric Rubin (editor-in-chief of NEJM), Eric Topol, and Robert Wachter (https://tinyurl.com/y946mw69). Thus, a “Who’s Who” of the medical academy dismisses life-saving therapy without a hearing.
Sep 29-Oct 2, 2021. 78th Annual Meeting, Pittsburgh, PA
Emergency Use Authorization
On May 1, 2020, on the basis of preliminary results from phase 3 trials, FDA issued an EUA to allow the use of remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adult and pediatric patients hospitalized with severe disease. The scope of the EUA was expanded on Aug 28, to allow use in a broader hospitalized population. On Oct 22, the FDA approved remdesivir for use in adults and pediatric patients (12 years of age or older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization (tinyurl.com/ya52ec49).
FDA has also issued EUAs for the Pfizer and Moderna vaccines, and for monoclonal antibodies—Lilly’s bamlanivimab and Regeneron’s casirivimab and imdevimab.
According to FDA (tinyurl.com/ycl2eb9j), “For FDA to issue an EUA, there must be no adequate, approved, and available alternative to the candidate product for diagnosing, preventing, or treating the disease or condition. A potential alternative product may be considered ‘unavailable’ if there are insufficient supplies of the approved alternative to fully meet the emergency need.”
If HCQ had been acknowledged to be an alternative treatment, then these new products arguably would not have qualified for an EUA. A shortage of HCQ was claimed, but FDA considered the shortage to have been resolved on Jun 26. It may be unavailable because pharmacists, for example by executive order from the Maryland Pharmacy Board, may refuse to fill prescriptions.
As Jeremy Snavely, AAPS director for regulatory affairs points out, FDA takes seemingly contradictory positions. How can both of these FDA statements included on the respective “Fact Sheets” for the Lilly and Regeneron drugs be true? (1) “There is no adequate, approved and available alternative to bamlanivimab for patients who have mild to moderate COVID-19 who are at high risk for progressing to severe COVID-19 and/or hospitalization.” (2) Same statement, replacing “bamlanivimab” with “casirivimab and imdevimab to be administered together.”
“So in other words, the FDA takes a very broad interpretation of what ‘adequate, approved, and available’ means in practice and bends the definitions to mean whatever the agency needs them to mean, or not mean, depending on its agenda at any given time,” states Mr. Snavely.
Maryland physicians who refer patients for infusions are required to document that the patient has been informed of the material in the fact sheet—and of alternatives. If the pharmacist refuses to fill prescriptions, that eliminates alternatives.
Portuguese Court Rules PCR Tests Unreliable
An appeals court in Portugal has ruled that the PCR process is not a reliable test for SARS-CoV-2, and therefore any enforced quarantine based on those test results is unlawful. The case concerns four tourists entering the country from Germany, who were quarantined by the regional health authority. One of them tested positive, and the other three were deemed simply of “high infection risk” based on proximity to the positive individual.
Judges Margarida Ramos de Almeida and Ana Paramés referred to several scientific studies, stating that when running real-time polymerase chain reaction tests with 35 cycles or more, the accuracy dropped to 3%, meaning up to 97% of positive results could be false positives. (https://tinyurl.com/y9ygldm6).
Conflicts of Interest
Ashish Jha. Dr. Jha is a senior advisor at Albright Stonebridge Group, which is affiliated with Albright Capital Management, an emerging markets investment firm founded in 2005. ASG describes itself as “the premier global strategy and commercial diplomacy firm. We help clients understand and successfully navigate the intersection of public, private, and social sectors in international markets.” Dr. Jha’s research centers on improving the quality and cost of health care. Supporters include the Bill & Melinda Gates Foundation, the Climate Change Solutions Fund, and the Commonwealth Fund.
STAT. This supposedly independent health news site, launched in 2015 by John W. Henry, owner of The Boston Globe, has a credibility problem due to pharmaceutical ghostwriting and authors with undisclosed industry ties, e.g. to Gilead Sciences (https://tinyurl.com/yalpz5w9). Its COVID-19 tracker looks at novel drugs and vaccines, not re-purposed old drugs.
Political conflicts. Papers from the U.S. concerning CQ or HCQ in COVID compared with non-U.S. studies were significantly less likely to have favorable results (10% vs. 33%) and more likely to have unfavorable results (57% vs. 33%). The names of U.S. main authors were entered into FollowtheMoney.org. Studies or editorials on CQ/HCQ, but not on non-CQ/HCQ COVID studies, were significantly more likely to have an unfavorable conclusion if the main author had donated to Democrats, suggesting that political bias is being injected into medical research and publication (https://tinyurl.com/yb4a34k4).
Tip of the Month: Old-fashioned medicine shines amid COVID-19: Long before expensive testing and experimental vaccines, medicine was practiced with our senses. It can take more than a day with significant inconvenience and expense to obtain a COVID test result, which can then be in error. But simply checking one’s sense of smell is a remarkably accurate sign of COVID. In a study in London, 80% of those who had lost their sense of smell had COVID antibodies, and in half of them it was their only symptom. Conversely, more than 80% of patients hospitalized for COVID had lost their sense of smell and taste, and for half of them it was their first symptom (tinyurl.com/y7zg7zd9). As early detection and treatment are essential to conquering the virus, old-fashioned medicine appears to be more efficient than high-priced testing. Screening with standardized olfactory testing could be a more effective means to contain infectious spread than molecular testing and to prevent lockdowns with their human and economic toll (tinyurl.com/ycb7qgoo).
Evidence for Vaccine Efficacy Challenged
Pathologist Sing Han Lee petitioned the FDA to stay the EUA for the Pfizer vaccine until sequencing tests on the 180 RNA samples are done to confirm their stated vaccine efficacy rate of 95%. The Pfizer/BioNTech vaccine trial primarily used an RT-qPCR test that employs cycle thresholds possibly up to 44.9 to identify “cases.” Samples requiring cycle thresholds greater than 30 to 35 are usually false positives, said Dr. Lee (https://tinyurl.com/ybnwh2le). A similar petition was filed with the European Medicines Agency by German epidemiologist Wolfgang Wodarg (https://tinyurl.com/y5wy7s96).
Remdesivir Conflicts. The most interesting part of the JAMA article that will be cited as showing “scientifically based improvement” in COVID patients (JAMA 8/21/20, tinyurl.com/y5tmj99j) is the “Article Information” in very fine print at the end. The study was sponsored by Gilead Sciences, the maker of remdesivir. At least 18 authors reported conflicts: grants, consulting fees, honoraria, travel grants, payment for serving on an advisory board for Gilead Sciences, and “personal fees.” Eight of the authors are employees of Gilead Sciences and own stock. The biostatistician was employed by Gilead Sciences. The conclusion: “Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance [emphasis added].” The design was “open label” (no blinding) because Gilead Sciences “had an insufficient number of placebo-containing vials to support this trial.” Authors admitted that “the ordinal scale used to evaluate outcomes was not ideal for detecting differences…, especially for a clinical situation in which discharge decisions may be driven by factors other than clinical improvement [emphasis added].” It sounds as though a conflicted investigator could improve the value of his Gilead stock simply by discharging a patient a few days early. The comparator was “standard care.” But, what is “standard care” for COVID-19 in hospitals, and is it the same in all 105 hospitals in the U.S., Europe, and Asia. Might some have used HCQ? So this is enough to declare a novel, costly drug the “standard of care”?
Lawrence R. Huntoon, M.D., Ph.D., Lake View, NY
RCTs in Psychiatry. As a psychiatrist, I note that the risk/benefit calculation for using antidepressants for a mild depressive disorder is not nearly as compelling as the case for using HCQ for COVID-19, yet it happens all the time. The same risk of QT prolongation occurs with many antidepressants. Show me the RCTs that support most of the way psychiatry practices.
Robert Berkowitz, M.D.., follow @truth_time4
A Fair Race. The randomized trials of HCQ are like a series of 100-yard dashes. Each time HCQ and control line up. The judge says GO and then he blows the whistle at 25 yards and says, “Mmmm, looks like a tie,” but in each race HCQ looks a little better than control. Then the “evidence” judge does the same thing again and again. If he would just let the race go to 100 yards, then the HCQ runner would win every time and by a substantial margin. The only way to handle these trials stopped early and the judges’ premature calls is to do a fair meta-analysis as done by Ladapo et al. (tinyurl.com/yakj4xzh). So even though the judge is not fair and each time declares “no difference,” the truth comes out in the meta-analysis. The race judge has nowhere to hide and should leave the field in shame and disgrace.
Peter A. McCullough, M.D., Dallas, TX
How Severe Is the Pandemic? COVID-19 data on Worldometers is not reliable. For example, a Portuguese court judgment highlighted the flaws of PCR tests. One way to do so is to look for the signal of the pandemic in total annual deaths. Sweden’s official agency recently updated its deaths data through Nov 13, from which I estimate that Sweden will likely report around 94,600 annual deaths in 2020. This can be compared with 92,185 deaths in 2018 (I’m excluding 2019, which had a very mild flu season across Europe). This shows Sweden will have had just 2,400 additional deaths in 2020. Sweden has had 6,340 reported COVID deaths to date. So where did almost 4,000 “COVID” deaths go? Most would be those who would have died during 2020 of some other cause. So if we factor in the natural variation of respiratory diseases then it is hard to identify any strong signal of the COVID pandemic. This data, which we can now start calculating for all nations, gives us a sense of the true magnitude of the severity of this pandemic. We can safely conclude that this pandemic’s lethality is far less than was imagined even a few months ago. Note also that many of the final annual deaths would be those caused by the lockdowns. The need to significantly downgrade the pandemic based on this analysis is particularly urgent since most of the world is still hysterical.
Sanjeev Sablokh, https://tinyurl.com/y9ftlxlp
Ethical Experimentation. Where is the institutional review board to oversee the massive country-wide experiment we are conducting with day-long masks often made of who-knows-what and made who-knows-where, substitution of screen time for each day normally spent in a schoolroom, and the unbelievably harsh social isolation of many of society’s more dependent people? I thought human trials required the oversight of such a board.
Pamela K. Grow, M.D., Rolla, MO
Bell Palsy. Pfizer has stated that the post-vaccination rate of Bell palsy was consistent with the background rate. Reportedly, the U.S. incidence of Bell palsy is 1/10,000 per year. But in the Pfizer trial, the 1/10,000 cases in trial subjects apparently occurred over the 2–3 month period of the trial, giving an annual rate of 4–6 times the U.S. average. [In the Moderna study, 4 of 30,000 developed this deficit, 3 of whom were in the vaccine group.]
Harvey Risch M.D., Ph.D., New Haven, CT