Learning to look at the evidence (1)

The debate rages on about ivermectin as a therapy for COVID-19. Given the devastation that the disease has caused, it is not surprising that the public may sometimes seek unconventional therapies. Substances such as vodka, cocaine, gasoline, volcanic ash, and bleach have been proposed as treatments, with some of these being clearly unsafe, and all of these remaining unproven to have benefit. It is not my objective to outline here the evidence for ivermectin. For these I direct the reader to the appropriate resources, including: the US FDA Statement on “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19”; the statement on the website of the Philippine Society for Microbiology and Infectious Diseases Inc. on “the Use of Ivermectin as Treatment for COVID-19,” a consensus by representatives of various medical societies; and the World Health Organization’s advisory “that ivermectin only be used to treat COVID-19 within clinical trials.” All of these, plus other documents by medical societies and health agencies, are available online. Rather, I hope to help the casual reader to understand the perspective of health professionals who raise objections to therapies due to insufficient evidence.

Most physicians in the Philippines are educated within a framework of evidence-based medicine. Under this framework, the care of individual patients is ideally based on the best available evidence combined with clinical experience, as well as patient values and preferences. The idea is to use the best available evidence results in safer, better, and more cost-effective health care.

Evidence is what allows doctors to make decisions that are more likely to avoid wasting patients’ money and time, and avoid putting them at undue risk. For example, a therapy for a given condition can point in one of several directions including: no effect; harmful effect; beneficial effect; or a combination of the latter two. These must be weighed by regulatory boards and physicians in their practices. Sometimes, we are limited by the fact that not all scientific investigations are published, and not all are done with the necessary rigor, which is why physicians should be equipped with skills to check evidence for strengths and limitations. Sometimes, evidence to answer a query is simply not available yet, which is why science is constantly evolving.

The strongest level of evidence for treatments comes in the form of systematic reviews of clinical trials, which are ideally done with randomization, with placebos (if appropriate), and with sufficient patient numbers. These and other steps are taken to minimize the likelihood that beneficial (or harmful or null) effects of proposed treatments are caused by individual factors. In contrast, we have types of evidence that are not considered robust or strong, such as patient testimonials, case reports, or series of case reports. This is not to say that reports of individual patients’ experiences are useless; rather, they require more intense investigation to verify that what is beneficial (or harmful) to a few may have the same effect on many, and in different population groups. This level of investigation often requires time, funding, expertise, and the support of patients and health institutions, which is why not all proposed therapies are quickly proven or disproven. Also, each drug formulation is tested rigorously, since not all preparations are equal or safe.

Dr. Jacinto Mantaring of the University of the Philippines College of Medicine and the Department of Health research ethics board described the results of ivermectin trials as “a moving target.” This underscores how interventions for COVID-19, including ivermectin, are not being dismissed; rather, out of concern for safety, cost effectiveness and benefit, most physicians will hesitate to recommend such products without a higher weight of supporting evidence.

In the case of vaccines, the reason that physicians vocally support COVID-19 vaccination is that these have met the standards of investigations to show that they are safe and effective in preventing different levels of illness. I have seen some supporters tout ivermectin as the “last hope” against COVID-19 while dismissing vaccines. Given the respective levels of evidence, to favor ivermectin while rejecting vaccines is, thus, unsound.

When physicians object to new treatments, they are accused of colluding with “big pharma” for financial gain, power, or some other nebulous motive. To think that the community would willingly withhold safe and effective treatment from COVID-19 patients is insupportable, as they are frontliners themselves who struggle amid full hospitals and understaffed ICUs and expose themselves to COVID-19 every time they go to work. Suspicion of doctors is yet another argument used to dismiss objections based on evidence, or lack thereof.

(To be continued)

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