In this series of critiques of Robert F. Kennedy, Jr.'s book "The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health," I left off discussing Kennedy's table of studies that show hydroxychloroquine is effective.
Continuing with the table on page 22. I had intended just to sample a couple of the cited studies. But then the first study was retracted. The second study didn't even look at hydroxychloroquine. The third study was never published.
So I continued to review the studies, one by one. In doing so, I intend to demonstrate that Kennedy is, in practically every detail, a liar who puts up phony evidence. When I'm done with the list of studies, I'll try to give an overall picture. How many were never published, how many that don't agree with what Kennedy presents, and how many the authors concluded that hydroxychloroquine doesn't work.
Here, below, is Kennedy's chart from page 22 of Chapter One of his book.
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| RFK Jr.'s list of "All thirty-two" studies with early intervention with hydroxychloroquine. |
(Continuing from my last entry.)
Nineteenth study. Guisado-Vasco. Kennedy correctly references 2 deaths in 65 patients (3.1%) who had taken hydroxychloroquine before admission and 139 out of 542 who did not (25.8%). However, remarkably, an additional 493 patients out of 607 total took hydroxychloroquine after admission to the hospital and 125 of them died (25.4%). If you add early hydroxychloroquine to later hydroxychloroquine, 127 of 558 died (22.8%). Of the 607 patients in the study, additional drugs taken include lopinavir/ritonavir (487), cyclosporine A (an immunosuppressant, 253), glucocorticoids (antiinflammatory and immunosuppressant, 159), and tocilizumab (an immunosuppressant and antiinflammatory, 132), the magnitude of the numbers saying that two or more drugs were taken. Tocilizumab and cyclosporine A were also deemed to have promoted survival to a statistically significant degree.
Twentieth study. Szente Fonseca. The Szente Fonseca study has a total of 717 patients with 334 receiving hydroxychloroquine (175 hydroxychloroquine alone and 159 hydroxychloroquine plus prednisone, a glucocorticoid), with 139 receiving prednisone alone, and 244 given neither prednisone nor hydroxychloroquine. Approximately half of all patients received azithromycin (53.3%) and/or ivermectin (47.4%) and/or oseltamavir (12.7%). To further confuse things, 65.7% of those in the category "hydroxychloroquine alone" received ivermectin and 42.9% were given azithromycin. A total of 122 patients were said to receive no medication, which would have made a good control, but they didn't report those results. All these categories and overlapping treatments (and lack of specificity as to how they overlap) really complicate making conclusions about what worked.
The results were given in terms of number treated who were hospitalized out of total number hospitalized. Hydroxychloroquine alone, 25 out of 114. Prednisone alone, 14 out of 114. Hydroxychloroquine plus prednisone, 16 out 114. Numbers were not presented for the other treatments, however, not having hydroxychloroquine or prednisone would have 59 cases out of 114. This study is a bit maddening on not identifying basic information that could help determine effectiveness, especially the question, what was the rate of hospitalization for the 122 patients with no treatment?
What does Kennedy conclude? 25/175 in the treatment were hospitalized versus 89 out of 542 in the control group. How did they get those figures? They seem to have considered hydroxychloroquine plus prednisone and every other treatment as part of the controls.
This study is a mess.
Twenty-first study. Cadegiani. Cadegiani, et al., looked at hydroxychloroquine, nitazoxanide (an antiprotozoal drug), and ivermectin, together with azithromycin. This is getting exhausting. If you want to prove something with certainty, stick to one thing, or two at the most. "Of the 585 subjects, all patients used azithromycin. A total of 357 patients used NIT [nitazoxanide], 159 used HCQ [hydroxychloroquine] and 110 patients used IVE [ivermectin], alone with azithromycin or in combination with other drugs." Several other drugs were mentioned as optional. Mercifully, Cadegiani describes the drugs taken in addition to hydroxychloroquine. All 159 patients on hydroxychloroquine took azithromycin, 21 also took ivermectin, 113 also took nitazoxanide, 86 also took spironolactone (an antidiuretic), and 7 also took dutasteride, an antiandrogen. I say mercifully because it is good for the sake of clarity, but it is impossible to pin down the role of hydroxychloroquine alone.
Kennedy presents the conclusion that 0/159 died in the hydroxychloroquine group and 2/137 in the control group. Cadegiani says that there was zero deaths in the treated population, all 585. He does not break out the numbers for the hydroxychloroquine treated patients, although zero is zero, which means that every treatment group and combination had zero deaths. Since the study had everyone treated, the control group of 137 were outside cases matched and added in.
Twenty-second study. Simova. Thirty-eight health care workers were found to be COVID positive. Half were asymptomatic. Thirty-three agreed to take azithromycin, hydroxychloroquine, and zinc. Five declined. Of the 33 who took the medication, none required hospitalization. Of the five who declined, two ended up being hospitalized. As an observational study, other than the small number of controls, this is not bad. It is a bias to allow the control group to define itself. Five of those taking hydroxychloroquine experienced prolonged heartbeat intervals (QTc intervals) which is a toxicity of the drug. They were discontinued from the treatment.
Twenty-third study. Omrani. There were three arms in this study, each with 152 participants. Azithromycin plus hydroxychloroquine, hydroxychloroquine alone, and no treatment. That would make for a good study design. Omrani presents the figure copied below as part of the results.
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| Placebo outperformed the drug treatments, although not to a statistically significant degree. p = 0.072 |
Omrani set viral recovery on day 6, virus below detection, and day 14 as the primary and secondary endpoints of their study. Kennedy reported hospitalization. Omrani looked at that outcome. "The HC+AZ [hydroxychloroquine plus azithromycin] and placebo groups each had four participants hospitalized (for each group, 2.6% of 152). The HC group had three participants hospitalized (2.0% of 152). There was no association between group and proportion of hospitalized cases (p = 1.000 by Fisher's exact test)." (emphasis mine) Researchers seldom get a p = 1.0, absolutely no support for their hypothesis (or technically, for rejecting the null hypothesis). Omrani, in his discussion, is very critical of the use of hydroxychloroquine and provides a survey of studies that it reject its usefulness.
Twenty-fourth study. Agusti. This study looked at 142 patients. Eighty-seven agreed to treatment with hydroxychloroquine. The controls consisted of those who declined treatment (43) and those who had contraindications to hydroxychloroquine (12). Kennedy says that 2 of 87 of those treated and 4 of 55 of those not treated made the endpoint of the study which he described as "progression." I'm not sure how he came up with his numbers. The study measured whether someone continued to be positive for the virus at days 7, 10, 15, 22, and 28 after diagnosis. Agusti found, "In conclusion, our study failed to show a substantial benefit of HCQ [hydroxychloroquine] in viral dynamics and in resolution of clinical symptoms. Treatment with HCQ was associated with a numerically higher percentage of negative PCR-tests at some points during follow-up in comparison with the non-treatment group, and a shorter duration of some symptoms was also seen with HCQ, but differences were only marginally significant and not clinically relevant."
Twenty-fifth study. Su. Although Su, et. al., does perform statistical analyses on their data, they do not provide the numbers of patients who were given particular treatments or how many improved compared those to controls. They don't even define controls. The conclusion from their statistical analyses are that "The early use of hydroxychloroquine decreased the improvement time and the duration of COVID-19 detection in throat and stool swabs."
Twenty-sixth study. Amaravadi This is another case of a paper that failed to be published. The preprint version is available. Early in the text there is this strange statement: "Out of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephone-based recruitment, but only 34 subjects were able to be randomized." and "Six randomized patients failed to complete the study leaving 28 patients for analysis of the primary outcome." and ". . . this study was terminated early due to lack of feasibility." That is just painful to read.
Twenty-seventh study. Roy. One problem with tracking down what Kennedy claims in his table is that he provides little information. For example, Roy. Which study is that? We have clues. It looked at recovery time (or did it? sometimes he gets that wrong), there were 14 in the treatment end and 15 in the control end. There is no published paper with Roy as the first author that includes the terms hydroxychloroquine and COVID. Okay, some of the studies Kennedy references were never peer reviewed and formally published. I finally found it.
Roy's paper is another one that does not exist outside of preprint. A total of 56 patients were divided into four groups. "1) having HCQ [hydroxychloroquine] 200 mg twice daily [14 patients] . . . 2) IVR [ivermectin] + DOX [doxycycline] . . . 3) AZR [azithromycin] and, the last group as per NIH guidelines who refused any treatment other than supportive treatment with antipyretics and oral rehydration solution. [15 patients]"
Roy's conclusion? "Mild COVID-19 infection in patients having low-risk to progress can be managed symptomatically without any specific drug intervention."
Twenty-eighth study. Mokhtari. My first impression: nearly 30,000 in a study. There are some quibbles with those numbers: 1898 were COVID test negative and another 4087 were not tested. Did they have COVID?
A major problem with the study is that "HCQ [hydroxychloroquine] was added to the supportive care for patients with mild COVID-19 illness who did not require referral to the hospital." This presents a huge bias: those who did not receive hydroxychloroquine were healthier. Kennedy reports 27 deaths out of 7295 in the hydroxychloroquine group and 287 deaths out of 21464 in the control group, consistent with Mokhtari's presentation.
Twenty-ninth study. Million. Looked at 10,429 ambulatory patients. Of these, 8315 were prescribed hydroxychloroquine and azithromycin. Zinc was later included as the study went along.
"The primary objective was to evaluate the age-specific 6-week IFR [infection fatality rate] of unselected adult outpatients infected with SARS-CoV-2 who were managed early in a dedicated COVID-19 day hospital offering standardized treatment based on HCQ+AZ. The secondary objective was to test whether the use of HCQ+AZ was associated with improved IFR and lower ICU [intensive care unit admission] and HC [hospitalization in a conventional ward] rates in this cohort."
So, Kennedy reported absolute death rates, 5 out of 8315 for those treated with hydroxychloroquine and azithromycin (plus or minus zinc), and 11 out of 2114 for those that weren't. If the ages of the two groups were equal, that would be in line with the study's goal. The study reported that no deaths took place in any patients who were under 60. It worked out to be that 18.0% of the treatment group were over 60 and 24.6% of the control group. Furthermore, this age difference became even more pronounced with older age with 5.9% of those in the treatment group being over 70 and 11.2% in the control group.
Adjusting for age, there was still a higher rate of mortality in the control group, but not nearly so dramatic as presented in Kennedy's numbers. As for the other two endpoints, hydroxychloroquine plus azithromycin did not reduce ICU or conventional ward hospital admissions to a statistically significant degree.
Thirtieth study. Sobngwi. A total of 95 patients receiving hydroxychloroquine were evaluated in comparison to 92 who received doxycycline, an antibiotic. All patients received vitamin C and zinc. "The primary endpoint was the rate of clinical recovery determined by the percentage of participants who became or remained asymptomatic. Key secondary endpoints included the percentage of participants requiring hospitalization due to worsening symptoms, as well as the proportion of participants displaying a negative SARS-CoV-2 PCR test."
Kennedy reported one of their findings, recovery at day 10: 4 had not recovered in the doxycycline group and 2 had not recovered in the hydroxychloroquine group, a result deemed insignificant (p = 0.44). From the paper: "In conclusion, we did not observe any significant difference in terms of safety and efficacy between doxycycline and hydroxychloroquine-azithromycin for the management of mild COVID-19."
Thirty-first study. Rodrigues. This study is interesting in that it is the only one among the 32 that Kennedy admits shows negative results, that is, not favoring the use of hydroxychloroquine. This is kind of harsh. Just like Kennedy's decisions to say that hydroxychloroquine worked where there was insufficient evidence, there is insufficient evidence here to say that it didn't work.
The patients were randomly assigned either hydroxychloroquine plus azithromycin or placebo.
"The primary outcome was the time to viral clearance within a 9-day evaluation period following enrolment after the onset of symptoms and the study enrolment dates. . . . Secondary outcomes of interest included: viral load reduction, improvement of symptoms, hospitalisation rates, and adverse effects to the trial medications."
Kennedy only reported hospitalization rates, saying 1 out of 42 in the hydroxychloroquine plus azithromycin group and 0 out of 42 in the placebo group. From the researchers' discussion: "In this randomised, double-blinded, placebo-controlled clinical trial evaluating outpatients with early and mild COVID-19 treated with HCQ/AZT or placebo, there was no benefit in the treatment arm on primary and secondary outcomes."
Thirty-second study. Sawanpanyalert. For the final study, there is a major problem. These researchers used chloroquine or hydroxychloroquine interchangeably and without distinction. These are not the same drugs. Hydroxyamphetamine is not the same amphetamine. Diacetylmorphine is illegal in the U.S. while morphine is not.
Their mix of drugs was complicated. "Among 533 symptomatic patients, 45 (8.4%) received CQ/HCQ alone [chloroquine or hydroxychloroquine], 10 (1.9%) received bPI alone [lopinavir/ritonavir], 197 (37.0%) received CQ/HCQ with bPI and 140 (26.3%) received FPV [favipiravir] with CQ/HCQ and/or bPI. Of 132 patients who received azithromycin, 121 (91.7%) also received CQ/HCQ."
The lack of identifying when hydroxychloroquine was used prevents evaluating it for this commentary.
So, there are thirty two studies. The problems with these.
Retracted: one.
Never published: four
Didn't include hydroxychloroquine or didn't identify what the results were for hydroxychloroquine: four. This number is being generous. Several more studies did not make clear what drugs were included in the hydroxychloroquine group versus control.
The authors state clearly that hydroxychloroquine was not shown to be effective: ten.
Studies with confidence intervals that negate a clear result: nineteen.
Studies that mix hydroxychloroquine with a second drug or third drug (or more) as part of the protocol: fourteen.
Many of the studies had hydroxychloroquine plus a second, third, or fourth treatment. These are problematic. Did hydroxychloroquine add anything to the therapy? Is it possible that the azithromycin, for example, did all the work? There was only one study that looked at hydroxychloroquine alone, hydroxychloroquine and azithromycin, azithromycin alone, and placebo. Several of the studies did not specify how many patients were receiving hydroxychloroquine alone versus hydroxychloroquine plus other treatments.
Earlier Kennedy had made the point that the lethality of COVID had been exaggerated. On page 5 of the first chapter, he said that even for the people hospitalized: "The real number [hospitalizations due to COVID] was less than one percent."
So what numbers does he show in his studies where hydroxychloroquine is cited as an early intervention (and not an intervention among those already hospitalized or critical)? There were twelve studies cited in the above table that had death as an outcome and which provided the numbers studied. (Excluding Bernabeu-Wittel (no totals to calculate percentage) and the study with the obtuse outcome of hospitalization/death). The control groups had the following as percent lethality:
40.0%, 2.9%, 3.4%, 9.1%, 26.4%, 4.5%, 53.3%, 1.5%, 25.6%, 1.5%, 1.3%, 0.5%.
Four studies had a death rate of over 25% among controls including one with over 50%. What the hell was going on in those studies?
To be continued.
Martin Hill Ortiz is a professor of pharmacology and author of several novels.
My new novel, The Missing Floor, is now available from Oliver-Heber books.
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| The Missing Floor, now available |
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