Posted by on November 24, 2020 3:59 pm
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By Erik Sass, TES Editor-in-Chief

 

There comes a time when a public figure’s statements are so wrong, so dangerous, and so grossly offensive that they must be rebutted and debunked one by one. This is the case with the Senate testimony and subsequent New York Times op-ed and media appearances by Dr. Ashish Jha, the dean of the School of Public Health at Brown University, concerning the critical area of COVID-19 treatment.  The chief falsehoods and distortions presented by Jha ­(who by his own admission has never treated a single COVID-19 patient) concern a few key subjects.

 

  • Jha disingenuously attempted to reframe the terms of the Senate hearing. Contrary to the purpose of the hearing, which was meant to address outpatient treatment, Jha cited studies concerning inpatient treatment for COVID-19.

 

  • Again contrary to the purpose of the hearing, which was supposed to cover a range of treatment options, Jha’s testimony focused narrowly – and deceptively – on one drug, hydroxychloroquine.

 

  • Jha’s repeated assertions that hydroxychloroquine shows no efficacy against COVID-19 are flatly false, as demonstrated by the testimony of other expert witnesses before the Senate, supported by scores of observational trials.

 

  • Jha’s attempt to dismiss evidence from observational trials as “anecdotal” is also false, as demonstrated by multiple large-scale studies showing that observational trials can anticipate the results of randomized controlled trials (RCTs).

 

  • Jha’s appeal to “evidence” from “high quality,” “rigorous” randomized control trials (RCTS) is yet another falsehood: all the RCTs conducted to date, and especially those cited by him, suffer from such serious errors of design and execution that they cannot be considered definitive in any sense.

 

While it is difficult to know where to begin, considering the sheer number of errors in Jha’s testimony, the simplest method is to address his Senate testimony chronologically. All times below refer to the video of the hearing hosted on CSPAN.

 

40:19: Jha stated that hydroxychloroquine has been “discredited through robust randomized controlled trials (RCTs).” 41:35 Jha stated that “every single high-quality study has failed to find any benefit of hydroxychloroquine for COVID-19.” At 42:40 Jha claimed that “Outpatient high quality randomized controlled trials” specifically showed no benefit for outpatients. At 45:00 Jha referred to the “Dismal failure of hydroxychloroquine to date.”

 

These statements are false, as demonstrated by a review of the RCTS cited by Jha himself, all of which suffer from major flaws. The titles of these studies and their main shortcomings are listed below:

 

 

Boulware D, et al. “A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. New England Journal of Medicine.” Published online August 6, 2020. doi:10.1056/NEJMoa2016638

 

  • Virtually total lack of PCR testing for COVID-19, with just 2.6% receiving standard tests, forcing researchers to rely on subjective self-reporting of symptoms
  • Treatment started an average of four days after COVID-19 exposure, rather than no later than two days as recommended
  • Included mostly low-risk individuals who generally do well without treatment
  • Not blinded: healthcare workers received identifiable pills
  • Study stopped prematurely, before statistically significant figures
  • Reanalysis shows the statistical significance of the large benefit of early treatment, contrary to the authors’ claims

 

 

The RECOVERY Collaborative Group. Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19. New England Journal of Medicine. Published online October 8, 2020. doi:10.1056/NEJMoa2022926

  • This study considered only inpatient treatments. It has no relevance to outpatient treatments, the subject under discussion.
  • Study was not a randomized trial; instead, the allocation of the drug was randomized, and the timing of drug administration varied widely
  • Median number of days from symptom onset [to treatment] was 9 days – far too late for early treatment effect.
  • Study suffered from “confounding by indication”: patients who received HCQ were already sicker than those who didn’t
  • Used dosage far exceeding recommended 2800 mg over six days

 

 

WHO Solidarity Trial (halted early)

  • In early October Dr. Soumya Swaminathan revealed that in the Solidarity trial hydroxychloroquine was often included in the standard of care comparator in many countries, requiring unknown and undisclosed “adjustments” be made to the data
  • The data from the Solidarity trial, and the nature of these “adjustments,” have never been published or revealed

 

 

Ulrich et al. Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients. Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446

  • Very small study, with 67 HCQ patients versus 61 control.
  • Suffered confounding by indication: patients receiving HCQ were 82% more likely to have very severe symptoms at the beginning of the study. HCQ recipients included 32% more males, who are known to fare worse on average.
  • HCQ recipients were also more like to suffer cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and have a history of organ transplants.

 

 

Fiolet et al., Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Clinical Microbiology and Infection. August 26, 2020.

  • Conflated hospital and outpatient studies.
  • Inclusion criteria required RT-PCR confirmed cases, but a number of studies included had negligible testing rates.
  • Authors do not consider different treatment delays, risk level of patients, differences in dosage, or usage of Zinc.

 

 

Magagnoli, Joseph, et al. “Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19.” Med (2020).

  • Not a randomized controlled trial at all. Suffered confounding by indication: choice of providing patients with HCQ was left to physicians, and cohort of 90 patients receiving HCQ prior to intubation were much sicker than the group of 177 patients not receiving HCQ prior to intubation.
  • Timing of treatment was apparently left up to the physicians as well, and the number of patients dying with and without ventilation indicates heavy “cross-over” to HCQ after patients were put on ventilators, and therefore much sicker; 75% of the patients not initially receiving HCQ prior to intubation were subsequently started on HCQ late in the clinical course, after they had deteriorated and required intubation.
  • Despite the supposedly negative conclusions of the VA study, just 7.8% of the initial HCQ patients later had to be intubated, compared to 14.2% of the other 177 patients not on HCQ who required intubation. In short, HCQ actually appeared to reduce the risk of intubation by 50% – even with bias favoring the non-intervention group.

 

 

Despite these numerous shortcomings, at 41:58 Jha stated there is a “clear consensus… based on overwhelming evidence” that hydroxychloroquine provides no benefit. In addition to the major errors discrediting the studies cited by Jha, his claim of “consensus” ignored the presence of  accomplished medical researchers at the same Senate hearing who presented evidence sharply contradicting Jha’s testimony, including Dr. Peter McCullough, Vice Chief of Internal Medicine at Baylor University Medical Center and Professor of Medicine at Texas A&M, and Dr. Harvey Risch, an eminent epidemiologist at the Yale School of Public Health.

 

In their testimony Dr. McCullough and Dr. Risch both pointed to scores of observational trials showing efficacy for HCQ against COVID-19.  However Jha scarcely addressed the subject, instead repeating baseless critiques of observational trials as compared to RCTs. Jha’s arguments against observational trials were based in large part on the false assertion that they do not provide an acceptable evidentiary basis for adopting a drug, which he claimed can only come from RCTs. At 43:40 Jha repeated the wholly false comparison of observational studies to hearsay, stating “Anecdotal evidence is not evidence.” This argument misrepresents the credibility of observational trials as a category, ignoring the existence of sophisticated techniques to counter biases in observational trials. At 43:05 Jha stated that observational trials “require control groups that are comparable.” However the requirement for comparable control groups has been met by multiple observational trials of HCQ vs. COVID-19 using methods like “propensity score matching.”

 

More broadly, Jha completely ignores the fact that large numbers of observational studies, considered together and subject to meta-analysis, are just as trustworthy as RCTs. One sweeping meta-analysis, drawing data from seven databases, compared more than 1,000 pairs of observational studies and RCTs across 228 medical conditions. It concluded that “on average, there is little evidence for significant effect estimate differences between observational studies and RCTs, regardless of specific observational study design, heterogeneity, or inclusion of studies of pharmacological interventions.” Another group of authors concluded that “the average results of the observational studies were remarkably similar to those of the randomized, controlled trials.” A third meta-analysis, reviewing 136 studies of 19 treatments, concluded: “We found little evidence that estimates of treatment effects in observational studies…are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials.”

 

On that note, observational studies subject to careful meta-analysis show strong support for HCQ as a COVID-19 treatment. An ongoing meta-analysis of 179 HCQ studies conducted in the U.S. and abroad (including 114 peer-reviewed, most of them observational) concludes: “Early treatment of COVID-19 with HCQ shows high efficacy.” The study authors provide detailed commentary on the strengths and weaknesses of the individual studies and their methods for accounting for bias in the study set.

 

Despite his own focus on RCTs, Jha ignored the findings of a meta-analysis of multiple RCTs conducted by Dr. Joseph Ladapo, a physician and health policy researcher at UCLA, with Dr. Risch and Dr. McCullough, showing substantial efficacy for HCQ against COVID-19. Addressing five RCTs covering a total of 5,577 patients, the study found a significant (24%) reduction in risk of negative outcomes using a composite measure of COVID-19 infection, hospitalization, and death. When the proper relationship of early HCQ use after COVID-19 exposure in one of the RCTs was used in the meta-analysis instead of all post-exposure use, the reduction in risk was substantially more significant (32%). The meta-analysis added that in these five RCTs, “Serious adverse events were not reported and cardiac arrhythmia was rare.”

 

Jha repeated false assertions about HCQ’s safety relating to potential heart arrhythmias. Regarding safety of HCQ in COVID-19 patients, a recently published study in the European Society of Cardiology’s journal, EP Europace, which considered only cardiac safety, found that short-term treatment was not associated with severe cardiac rhythm disorders in patients with COVID-19 under appropriate surveillance. The study concluded: “HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.”

 

Perhaps most damning for his own credibility, Jha also presents drug statistics in a disingenuous, misleading way. He notes that in the months after hydroxychloroquine first emerged as a treatment option, “we saw a 93% increase in hydroxychloroquine and chloroquine exposures reported to the U.S. Poison Control Centers, compared with April of 2019, presumably due to the large number of people taking hydroxychloroquine for COVID-19.” However Jha doesn’t provide the actual numbers behind these proportions: in fact the total number of calls were under 100, out of approximately 500,000 additional hydroxychloroquine courses delivered during this time – for a less than 0.02% incident rate.

 

These are just a few of the myriad errors, distortions, and misrepresentations undermining Jha’s testimony to the Senate. Indeed, a full accounting would require a book. But as this quick review shows, Jha’s misleading and deceptive statements about a life-and-death matter with relevance to millions of Americans in his testimony to the Senate hearing (and in his numerous media appearances) are an embarrassment to himself and his institution. Indeed they are, as Dr. McCullough himself stated in rebutting Jha, “wrong and dangerous for the country.”

 

 


Erik Sass is editor-in-chief of The Economic Standard.