Rabat – The unfathomable impact of the COVID-19 global pandemic has left medical experts racing to discover a cure for the virus and exploring already-on-the-market drugs such as chloroquine and hydroxychloroquine.
The clinical trials and research surrounding the prescription drugs’ effectiveness against COVID-19 have prompted serious debate, while big pharmaceutical companies fatten their wallets with the promise of a much depended upon solution to the world’s present woes.
Chloroquine has been in use since 1934 and has traditionally been prescribed as an antimalarial agent, as well as to treat HIV-1 infected patients. It has also been used in treatment for some autoimmune diseases.
Its derivative, hydroxychloroquine, is less toxic and has been used to treat lupus erythematosus and rheumatoid arthritis.
As both drugs undergo investigation, efforts to understand and propagate or forgo the drug have sparked controversy. This led many to question the means and motives of those responsible for the need to discover imminent preventive tools and cures.
A timeline of studies: The Lancet’s push and pull on Chloroquine
The Lancet, one of the world’s most prestigious peer-reviewed medical journals, has published numerous articles documenting research surrounding chloroquine and hydroxychloroquine. Medical scientists, clinicians, and bioethicists have warned that as pressure builds to discover a cure, guidelines that patrol the ethics and transparency of critical data are falling by the wayside.
Skeptics of the most recent Lancet publication have cited a number of methodological concerns and data integrity issues, leading many to retrace historical reports and data surrounding the drugs’ relative safety and uses.
A 2003 study hypothesized that chloroquine and hydroxychloroquine could be beneficial in treating forms of coronavirus such as SARS. The study even made mention of the looming threat of a worldwide contagion, a possibility that scientists have touted for years under increasingly exploited ecosystems and mostly fragile healthcare structures around the world.
“We raise the question of whether this old drug whose parent compound, quinine, was isolated in the late 19th century from the bark of the tropical cinchona tree, may experience a revival in the clinical management of viral diseases of the era of globalization.”
The study affirmed, “The use of chloroquine/hydroxychloroquine in rheumatic diseases and for antimalarial prophylaxis showed a low incidence of adverse events during chronic administration of this drug for periods of up to a few years.” The researchers added, “A recent study provided encouraging results on the safety of a high dosage of the drug (up to 500 mg of chloroquine base per day) even during pregnancy.”
In-vitro studies, which are test-tube experiments or tests done with biological molecules outside of their normal biological setting (i.e. the human body), were published in the 2006 article confirming earlier hypotheses. These results led researchers to push for further exploration that might lead to developing strategies and vaccines that would control several viruses, including strains of coronavirus.
“Our hypothesis that chloroquine might inhibit replication of the SARS coronavirus has been confirmed in two independent in-vitro studies,” the 2006 study explained regarding experiments carried out in Belgium. “The broad spectrum antiviral effects of chloroquine deserve particular attention in a time in which the world is threatened by the possibility of a new influenza pandemic, and the availability of effective drugs would be fundamental during the evaluation of an effective vaccine.”
Researchers noted that patients must only consume correct dosages of the drug, and that if not monitored correctly, side effects may include impairment or loss of vision.
The latest report
More recently, clinical trials performed on patients desperate to be cured of the novel coronavirus have issued new and contradictory findings, ones at which a number of researchers and medical professionals are raising their eyebrows.
On May 22, the Lancet released results of a study stating that medical experts were unable to confirm the benefit of the two drugs in this context. The study, which claimed to be an observational account of 96,032 hospitalized COVID-19 patients from six continents, concluded that patients on related drug regimens were “associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.”
In response to the publication, the World Health Organization (WHO), responsible for leading the global response in the fight against COVID-19 and facilitating and funding worldwide research on its behalf, immediately halted all uses of the drugs under the recommendations of the recent publication. Independent of the WHO-backed worldwide research teams and testing, treatment and prevention stakeholders in the UK and France have also issued the suspension of relevant trials.
“Concerns regarding the statistical analysis and data integrity”
More than 120 leading medical professionals and researchers from around the world have signed an open letter to the authors of the most recent study expressing their concerns.
The letter states, “There was inadequate adjustment for known and measured confounders (disease severity, temporal effects, site effects, dose used).”
It also explains that the authors adhered to a number of irregular practices including: Not releasing their code or data, a total lack of ethics review, and a failure to cite the countries or hospitals that contributed to their data, with zero acknowledgments of their contributions.
Australian medical professionals indicated that Sugisphere, the healthcare data and analytics company responsible for compiling the Lancet study’s data, significantly overcounted the number of in-hospital deaths that had occurred within the country.
Sugisphere’s founder and co-author of the Lancet’s paper, Dr. Sapan Desai, claimed that the numbers are legitimate and the error was attributed to an incorrect classification of hospital deaths. In fact, Dr. Desai claimed, the extra number of deaths attributed to Australian hospitals were actually tied to a hospital in Asia.
A dangerous lack of transparency
Many are not convinced by Sugisphere’s assurance. “If they got this wrong, what else could be wrong?” said Dr. Allen Cheng, epidemiologist and infectious disease doctor at Alfred Health in Melbourne. Cheng noted that he had never heard of Surgisphere and he believes that nobody at Alfred had provided the data company with their records.
The letter also reports concerns surrounding data gathered from hospitals in Africa and questionably small variances in baseline variables, interventions, and outcomes between continents.
Despite authors of the study reporting that 66% of the data was gathered from North American hospitals, the mean daily doses of hydroxychloroquine were 100 mg higher than the US FDA-approved recommendations.
Questions regarding the unusually small number of authors and the total lack of published peer review, as well as the authors’ refusal to make the dataset public or subject to statistical review, has alarmed many due to the enormous influence of these results.
The signatories of the letter to the Lancet requested transparency in the form of openly available peer review comments that pushed this study into publication.
Although Surgisphere has stated that their data is collected and “transferred in a de-identified manner,” the company has also refused to release the data. “As with most corporations, the access to individual hospital data is strictly governed. Our data use agreements do not allow us to make this data public.”
Skepticism beyond the release of the Lancet’s data
Some of the signatory doctors have stated that the problems tied to the research paper do not support the hypothesis that chloroquine is safe or effective in treating COVID-19. Many are simply seeking full transparency and the right to uphold a system of peer review in the name of medical sciences — not to mention a desire to ensure that the energy and resources put forth to address the worldwide pandemic are not wasted.
While some have cautioned against the continuation of trials, there are a number of doctors and researchers standing by the promise of chloroquine/hydroxychloroquine and hoping to further explore its uses.
Morocco’s Minister of Health Khalid Ait Taleb has stressed the extremely low number of deaths within the country, attributing the statistics to the healing properties of the drug. On May 28, the minister informed the House of Representatives of the country’s success using chloroquine to heal patients.
As of May 30, Morocco has counted 7,780 confirmed cases of COVID-19, including 5,401 recoveries and 204 deaths. Ait Taleb clings to the sovereign decision to proceed treating patients with the drug, reiterating that it has prevented mass deaths.
Also skeptical about the Lancet’s hazardous claims and the WHO’s quick support in pulling the drug off the table, Ait Taleb added that the prior to the onset of COVID-19, the use of chloroquine was considered safe, and there were no known deaths related to treatments with the drug.
A French physician and microbiologist specializing in infectious diseases, Didier Raoult, insisted that the Lancet’s publication was faulty, lacking the use of a control group and avoiding proper protocol.
Controlling the system
Although many have dismissed Dr. Raoult for his unorthodox approach to medicine, it may be more difficult to argue against the influence that pharmaceutical companies have over politicians and in turn, the world’s leading approach to battling the pandemic.
Skeptics of the new world order remind us that pharmaceutical companies hold the highest position of political power in terms of lobbying in the US. In 2019, drugmaker lobbies spent more than $129 million through the end of September alone. Some prescription drug companies spent record-high sums lobbying congress last year.
Lobbying, a tactic for persuading the interests of legislators on particular issues, can be a productive form of educating the government on critical issues. However, the ethics of wrapping lifesaving research, healthcare systems, and medical resources up in millions of dollars tied to political agendas are far from sound.
As countries around the world continue to enforce stay-at-home orders, grapple with new social distancing measures, and sink into deeper financial struggles, people awaiting a solution remain bonded to a system that further equates power with big-spending corporations.
*The use of chloroquine/hydroxychloroquine or any other drug should not be taken without consulting doctors.