The tools for defeating quackery
Why we need randomized controlled trials (RCTs) to find the best ways to treat COVID-19.
By now, it’s common knowledge that the disease known as COVID-19 has left a trail of suffering and death across the world. At best, life as we know it has ground to a halt with no guarantee of it ever returning to normal. People are desperately searching for answers, waiting for scientists to find the breakthrough treatment, cure or vaccine. In this moment of uncertainty, pseudoscience and quackery proliferate.
There’s no shortage of pundits. Everyone from clinicians to religious leaders to the president of the United States have offered their opinions on what is the best course of action in the face of COVID-19. There’s a long list and depending on who you follow, the disease could be eliminated by: ingesting bleach; high doses of Vitamin C; Zinc; a combination of Azithromycin (antibiotic) and Hydroxychloroquine (anti-malarial); Madagascan medicinal plants; the BCG vaccine given to babies to prevent severe forms of Tuberculosis (TB); avoiding telecoms masts or inhaling a nebulized silver solution. Some of these claims are backed by limited anecdotal evidence of recovery in patients diagnosed with the virus. The problem however with evidence outside of a clinical trial is that it’s not known whether these patients simply recovered on their own or for other reasons, regardless of treatment.
That’s why it’s important to understand the purpose of a clinical trial. COVID-19 is an emerging and rapidly evolving situation that challenges and does away with a lot of existing knowledge as new information arises on a frequent basis. Without a framework for interpreting this information and an understanding of what constitutes scientific evidence, there’s a risk of being swept up by unsubstantiated claims that are potentially life-threatening if acted upon—such as ingesting bleach.
Randomized controlled trials (RCT) are not an obstruction to knowledge but an attempt to rigorously evaluate evidence and eliminate associated biases. In a clinical RCT, individuals with the same illness are randomly assigned to different treatment groups. One or more groups, depending on the size of the trial and the number of interventions being tested, may receive a new form of therapy while a control group receives a placebo or the standard of care. The outcomes are then compared between the groups to determine if there is any actual therapeutic effect. It’s the randomization of participants to treatment groups that’s one of the main reasons RCTs are referred to as the “gold standard” of study designs. Randomization avoids confounding the results with known and unknown factors about participants, it ensures that the presence of these factors is evenly distributed in each group and that every participant has an equal chance of receiving the treatment. There is much oversight that goes into a clinical trial, especially when testing new drugs or treatment options.
One of the American doctors given a lot of airtime for using Azithromycin and Hydroxychloroquine to treat COVID-19 patients openly stated that given the urgency of the situation, there was no time to wait for trials. He claimed his adapted cocktail, based on findings from Chinese and French studies, showed incredible success rates among his private patients. Without a comparison group, it’s unknown whether or not these patients truly responded to the treatment, if they were simply healthier, less severe cases or if the doctor chose patients that he thought would do better on the treatment. It also calls into question the way in which consent was obtained from patients given that this medication had not been properly tested and for which there is still insufficient evidence for or against its use in COVID-19. An ethical protocol developed by the World Health Organization (WHO), known as Monitored Emergency Use of Unregistered Interventions (MEURI), does exist for the “compassionate use” of unregistered treatments during public health emergencies. It was updated most recently during the 2018 Ebola outbreak in the Democratic Republic of Congo for use for a number of investigational therapies at the time. But it’s not a protocol that can be spontaneously invoked based on a clinician’s personal judgement. It requires approval from country authorities, ethics committees and informed consent from participants.
When there is limited understanding of evidence-based practice among health professionals, even the most well intentioned among us are vulnerable to being deceived, buying into anecdotal evidence or equating laboratory findings in animal cells to real world outcomes in human beings. Ideally, health professionals should be equipped with an ability to critically assess evidence in ways that allow them to primarily give the best advice to their patients and weigh in on debates without polarizing their input or feeling affronted when individual experiences are challenged. And health policies and clinical guidelines should be based on credible RCTs conducted in settings that closely resemble where the findings will be applied, to maximize effectiveness.
For many poor and low-income countries, the barriers to achieving this are enormous. For starters, specialist research or epidemiology training are often not prioritized due to the demand for clinical skills and experience. As a result, those with the means and desire, migrate to countries that offer such training and in doing so contribute to a brain drain in their home countries. Access to online quality accredited skills development is also prohibitively expensive. Research is chronically under-funded, and if no local source of funding is found, then researchers rely on donor agencies or pharmaceutical companies that don’t always align with local research priorities. Economic globalization has also made clinical research in poor and low-income countries more attractive because it’s cheaper. Everything from participant reimbursements to research staff salaries costs much less than in a developed country. In addition, the high disease burden and relatively treatment naïve population, either untreated or under-treated, means they’re more likely to respond to treatment as opposed to being refractory. Some reports have shown that only a fraction of new drugs being tested is of any relevance to the burden of disease in these countries. TB is a case in point; more than 95% of cases and deaths occur in developing countries, and prior to 2013 when Bedaquiline was registered for use in treating drug-resistant TB, no new drug had been developed for over 40 years despite the growing threat of multi-drug resistant strains. Traditional medicine is even further off the radar of clinical trials despite the World Health Organization reporting its use in up to 80% of African populations, especially in places where western medicine is not widely available.
RCTs require intense planning and a significant amount of expertise. Poor and low-income countries fundamentally lack the capacity to conduct high quality, rigorous research yet suffer a massive burden of infectious diseases and a rapidly rising prevalence of chronic diseases. Unlike TB, COVID-19 doesn’t discriminate and the global pandemic has allowed for global action in the form of the “Solidarity” trial, launched by the WHO and partners on March 18, 2020. “Solidarity” is enrolling patients with COVID-19 in multiple countries and testing four treatment options against the standard of care, to determine if any of these drugs show promise of slowing the disease progression or improving survival. It’s unclear exactly which countries are participating but the WHO “Solidarity” webpage claims that “as of April 21, 2020, over 100 countries are working together to find effective therapeutics via the trial.” South Africa was one of the first countries to formally join the trial and the first African country with reports that Senegal and Burkina Faso are in the process of enrolling. More and more calls are being made to increase representation from Africa to ensure findings from this trial have relevance on the continent and take into account differing health characteristics, co-morbidities and socioeconomic factors of African populations.
While the continent’s inhabitants are often stereotyped by images of poverty, malnutrition, disease and lack of access to basic services, African countries are not homogenous. Some have moved ahead with their own clinical trials using Hydroxychloroquine, immune boosters and even traditional herbal medication. Like everything about COVID-19 at this point, it’s too early to say what will come of these efforts. Perhaps it will lead to a ground-breaking synergy between modern science and traditional African medicine, perhaps it will be a painful lesson in experimentation. In the meantime, as the world waits for concrete tried and tested solutions to emerge, understanding how to navigate the tide of information could limit the damage caused by desperate attempts to control the outcome.