There are currently no approved therapies for the treatment of coronavirus disease 2019 (COVID-19). With an array of potential treatments
under investigation, clinicians are torn between the imperatives to provide care and to practice evidence-based medicine.
In a recently published commentary in JAMA,
Derek C. Angus, MD, MPH, a professor at the University of Pittsburgh School of Medicine, argues that the gradual pace at which we research other health challenges is not suited for a pandemic which has shut down society’s non-essential functions.
Angus opines that the best approaches in science is to blend learning with doing.
However, the commentary elaborates that medicine is organized to do these tasks separately. Clinical practice (doing) and clinical research (learning) are addressed by disparate institutions, procedures, and funding.
Hospitals and clinician groups practice medicine while public institutions like the National Institutes of Health, academic institutions, and pharmaceutical companies focus on scientific exploration.
“There are many reasons for this division of labor, not the least of which was the Belmont Report
, which codified that research should be kept separate from the practice of medicine, or patients’ interests will be usurped,” Angus writes.
If contemporary medicine interprets the ethical principles laid out by the Belmont Report
to require this division of labor institutionally, achieving greater ethical priorities for patients may be the cost.
Angus acknowledges the perils involved in attempting to bridge the divide between practice and scientific discovery. The most powerful weapon in the learning arsenal is the randomized clinical trial, but randomization can be uncomfortable.
For example, a conventional randomized trial would require clinicians who believe a COVID-19 patient would benefit from hydroxychloroquine
to potentially withhold the treatment in some cases. From an academic perspective, this is responsible because an investigational treatment might actually turn out to be harmful.
Initiating a randomized clinical trial is also expensive and requires coordination between institutions.
“Although well-motivated, the entire clinical trial enterprise—investigators, drug companies, and funding agencies—is currently in worldwide chaos,” Angus notes.
To solve these problems, Angus suggests a cooperative international effort to adapt trials to the pandemic. The community can promote designs which make randomization more comfortable, assigning more treatment options and dosages to reduce the proportion of patients who need to be in control groups. Trial designs can also be simplified. Placebo groups can introduce new levels of logistical and interpretive complexity at a time when the perfect cannot be the enemy of the good.
While collaboration will be impeded by the absence of a common platform to combine local system electronic health records, health care systems could implement study logistics into clinical information systems as much as possible.
Physicians can also communicate with patients wisely on this issue, given their understanding that for a new disease, any treatment administered is experimental.
If we can synthesize the way we conduct clinical trials with practice, we can both learn more and do more. More practitioners can be confident about giving critically ill patients an investigational treatment, and instead of the risks involved meaning nothing if the drug fails, we will move treatment development forward.
“If the problem of learning while doing cannot be solved, the period until effective treatments are discovered and implemented will be prolonged, in turn prolonging the period that society must endure these blunt public health measures,” Angus concludes.
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