The Complexity of Scientific Studies: Remdesivir and Hydroxychloroquine

The scientist does not study nature because it is useful; he studies it because he delights in it, and he delights in it because it is beautiful. If nature were not beautiful, it would not be worth knowing, and if nature were not worth knowing, life would not be worth living. (Jules Henri Poincaré, French mathematician, theoretical physicist, engineer, and philosopher of science.)

It appears that hospitals have another weapon to reduce the risk of people being hospitalized with COVID-19. As Pharmacy Times reports, “Intravenous (IV) treatment with remdesivir [Veklury] . . . significantly reduced the risk of hospitalization in high-risk patients who were diagnosed with COVID-19 but were not hospitalized, according to the results of a double-blind, placebo-controlled study.” 

In the study, researchers analyzed 562 participants who were randomly and equally assigned to receive either remdesivir, Gilead Sciences Inc’s intravenous antiviral drug, or a placebo. According to Reuters, “The 562 patients in the study all had conditions that increased their risk for becoming critically ill.”

A press release by Gilead stated, “Veklury demonstrated a statistically significant 87% reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) p=0.008.”

Moreover, Gilead’s study  “showed an 81% reduction in risk for the composite secondary endpoint of medical visits due to COVID-19 or all-cause death by Day 28 for participants treated with Veklury (1.6% [4/246]) compared with placebo (8.3% [21/252]) p=0.002.”

Taken all together, then, remdesivir reduced not only hospitalizations but also the need to obtain medical visits as well, thus reducing the strain on an already stressed medical system. 

Remdesivir may also show promise for patients that are already hospitalized due to COVID-19 complications. In a press release, Robert L. Gottlieb, MD, PhD, cardiologist and principal investigator at  Baylor University Medical Center, said, “Antiviral medications provide maximal benefit when used early in the disease course,” adding “Last summer, data from clinical trials demonstrated the benefit of remdesivir in patients hospitalized with COVID-19, even when not yet requiring oxygen. These latest data show remdesivir’s potential to help high-risk patients recover before they get sicker and stay out of the hospital altogether.”

The findings contradict a previous study commissioned by the World Health Organization which studied the effectiveness of remdesivir, hydroxychloroquine, lopinavir, and interferon in reducing the severity, progression, and morbidity of COVID-19 complications. The researchers concluded, “These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.” 

Remdesivir, an antiviral drug, has been found by a new study to reduce complications that would lead to hospitalizations.


There is reason to believe that, at least with hydroxychloroquine, the same dynamics were at work. Worse still, it was a potentially politically motivated scenario. At the beginning of the pandemic, Dr. Harvey Risch, professor of epidemiology at Yale’s School of Public Health, wrote about his concern that he was “flummoxed” to find himself “fighting for a treatment that the data fully support but which, for reasons having nothing to do with a correct understanding of the science, has been pushed to the sidelines. As a result, tens of thousands of patients with COVID-19 are dying unnecessarily.”

As Heather E. Heying, an American evolutionary biologist, so eloquently observed, “Science functions best when all hypotheses are on the table. Some will be easily dismissed. Others will prove recalcitrant to falsification, even if we eventually come to understand that they are not true. But what science needs, above all else, is the freedom to discuss the possibilities. Without that, there will be no new discoveries.”

In July of 2020, another study published in the International Journal of Infectious Diseases found the  “use of hydroxychloroquine + azithromycin was associated with a 66% reduction in risk of death as compared to controls; the analysis also suggested more substantial effectiveness of hydroxychloroquine in patients with less severe COVID-19 disease.” 

In yet another study conducted by Henry Ford Hospital, the researchers concluded, “treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality.” 

But support for using or advocating for hydroxychloroquine comes with a steep price, as Dr. Todaro found out.

According to the Children’s Defense Fund, “On March 13, 2020, Dr. Todaro and a coauthor published an online white paper that pointed to the CDC’s 2005 chloroquine research and outlined the early and successful use of CQ in Covid-19 patients in South Korea and China. Noting these promising results and the fact that China had zeroed in on CQ ‘after several screening rounds of thousands of existing drugs,’ the two physicians urged the U.S. to give America’s medical profession an immediate green light to prescribe CQ and HCQ for Covid-19 patients. Instead, the doctors were met with Google’s removal of their white paper.”

While it would be fair to point out that not everyone will respond to hydroxychloroquine, the extant literature suggests that in certain cases, hydroxychloroquine alone or in combination with other medications, made a significant contribution to the reduction or the progression of the severity of complications related to COVID-19.

The fact that the conclusions of the studies contradict one another is not surprising. David Penning, an assistant professor of biology at Missouri Southern State University, points out, “This is exactly how science works,” adding, “I can understand the frustration from the public, because they see changes of opinion fairly quickly. But that is what’s supposed to happen.”

In fact, the validity and reliability of findings from scientific studies may not be as solid as many people are led to believe. This is important because replication is an indicator that the study was well constructed, carefully administered, and objectively analyzed. As Timothy Errington of the Center for Open ScienceSuccessful argues, “replication provides evidence of generalizability across the conditions that inevitably differ from the original study; unsuccessful replication indicates that the reliability of the finding may be more constrained than recognized previously.”

Yet many studies, fail in their efforts to be replicated by other researchers, leading to a phenomenon known as “the replication crisis.” The replication crisis is exactly what it sounds like: an inability of subsequent scientific studies to replicate, or reproduce, the findings of previous studies. Consequently, The Reproducibility Project (RP) was created.

As reported in the academic publication, The Conversation, RP consisted of  “a collaboration of 270 psychologists,” which “attempted to replicate 100 psychology studies, while a 2018 report examined studies published in the prestigious scholarly journals Nature and Science between 2010 and 2015.” RP found that, “about two-thirds of studies do replicate to some degree, but that the strength of the findings is often weaker than originally claimed.”

Hydroxychloroquine, an anti-malarial medication, became a lightning rod for controversy regarding its effectiveness as reducing COVID-19 complications and morbidity Source:

This has become a sticking point in scientific research circles, and likely subtly undermines the confidence of the public in scientific data. According to the BBC, Marcus Munafo, now a professor of biological psychology at Bristol University, experienced this personally as a graduate student when he failed to replicate an experiment from a textbook.

His failure almost led to him giving up on his graduate work. But in reality, it wasn’t Munafo’s fault, but rather a reflection of a phenomenon of curation bias. As Munafo explains, “What we see in the published literature is a highly curated version of what’s actually happened. The trouble is that gives you a rose-tinted view of the evidence because the results that get published tend to be the most interesting, the most exciting, novel, eye-catching, unexpected results. What I think of as high-risk, high-return results.”

This would make lead most people to conclude that the studies were deeply flawed, and therefore their findings would be rendered unreliable. Some people might even be suspicious that fraud is at play, which is always a sinister possibility lurking in the background. 

But the further you explore this issue, the muddier it gets, unfortunately. As Oswald Steward of the Reeve-Irvine Research Center at the  University of California, Irvine, California states, “The first thing to emphasize is that a failure to replicate doesn’t mean that there is any suspicion of scientific misconduct. A failure to replicate a study published in a peer-reviewed journal simply means that similar results were not found. There are many reasons why this may be the case including that the initial study is correct and the replication study is flawed. Thus, a failure to replicate is simply a call to attention that there is a discrepancy.”

For consumers, this can be overwhelming when trying to make decisions about medical care. Which study is correct? Are the researchers legitimate academicians? How well constructed was the study? Is there evidence of bias? 

As a journalist who reports on a variety of scientific topics, with a special emphasis on medicine and health, I can give one small bit of advice: read the results of the original study, not the condensed, often incorrectly interpreted reduction of other journalists and writers. If they provide a link to the original study, follow it and read the documents they are citing.

In a recent article I wrote about the consequences of legalizing marijuana, I discovered the analysis of a CBS article I found superficial and lacking context, and the headline at best misleading, if not completely inaccurate, once I read the original study they cited. Sometimes this means doing multiple searches for the original study, but it’s a worthwhile effort. 

If you really want to understand the findings of an article, you may want to read the suggestions of this publication from the National Center for Biotechnology Information (NCLB). Meanwhile, be careful of your sources of information, especially sources that float through the miasma of social media, which are often decontextualized and repackaged to fit an existing schema and political orientation. 

Ultimately, the practice of medicine is anything but an exact science. It requires judgment based not only on scientific knowledge, which is continually evolving, but simultaneously an ability to integrate empiricism with rational deductions tempered by experience, the cognitive mediator that physicians rely on to make informed decisions for their patients.

Whether they are treating a patient for cancer, or for COVID-19, they blend best practices based on scientific data with empirical observations and experiential knowledge. In essence, over time, physicians develop a personal philosophy of practice, of how they approach patient care, based on their trials and tribulations with real patients in real-time, not just the input of a myriad of seemingly contradictory studies.  As Aelius Galenus, Galen, a Greek physician, surgeon, and philosopher in the Roman Empire so aptly put it: “The best physician is also a philosopher.”