|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 51-52
Evidence, end-points, and epistemic - Handling the uncertainty of COVID-19-related infodemic
M Shuriya Prabha1, V Dinesh Kumar2
1 Department of Paediatrics, Rajah Muthiah Medical College and Hospital, Chidambaram, Tamil Nadu, India
2 Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
|Date of Submission||15-Aug-2020|
|Date of Decision||21-Nov-2020|
|Date of Acceptance||02-Feb-2021|
|Date of Web Publication||02-Jul-2021|
V Dinesh Kumar
Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry,
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Prabha M S, Kumar V D. Evidence, end-points, and epistemic - Handling the uncertainty of COVID-19-related infodemic. J Curr Res Sci Med 2021;7:51-2
|How to cite this URL:|
Prabha M S, Kumar V D. Evidence, end-points, and epistemic - Handling the uncertainty of COVID-19-related infodemic. J Curr Res Sci Med [serial online] 2021 [cited 2021 Dec 5];7:51-2. Available from: https://www.jcrsmed.org/text.asp?2021/7/1/51/320505
One of the collateral effects of the unprecedented COVID 19 outbreak is the maelstrom of related research publications and this explosion is not free from skewed information and premature hoaxes. In their recent letter, Pieralli et al. mentioned this phenomenon of “emergency and emotionality” as the eighth alternative of evidence-based medicine. We had witnessed a weakly designed study suggesting the utility of hydroxychloroquine, involving a non-randomized sample of 46 patients, got published as a preprint and circulated widely in social media with more than 520 citations in databases though getting critiqued by experts with genuine concern. The never before experienced state of “peer review lenience” and urge to do something coupled to create a state of “epistemic exceptionalism” whereby the practitioners swayed to the weak, skewed claims with significant methodological compromises and ambiguous end-points without being keen about the potential harms of drug interventions.
One of the serious intrinsic confounders to the credibility of the research findings is the framing of the objective endpoints and justifying/refuting the efficacy of the drug based on these stringent parameters (aleatory and epistemic uncertainties). In the case of COVID-19, it took considerable time for deciphering the objective endpoints which include effect on mortality, need for mechanical ventilation, time for clinical improvement, period of hospitalization, and adverse events related to administering the chosen drug. Incidentally, out of these end-points, the term “clinical improvement” is based on an ordinal scale, and “period of hospitalization” depends on other independent variables as well. These landed the practitioner in ambiguity, one of the types of uncertainty, which can be defined as the situation when expert clinicians tend to disagree over the possible time frame, drug options, outcomes, and harm-benefit quotient.
In contrast to ambiguity, fundamental uncertainty is an uncertainty whereby decision needs to be made even before concrete evidence are available. For example, let us consider the widely debated drug of the day, Remdesivir. The foremost placebo-controlled trial related to the use of Remdesivir in COVID-19 patients couldn't document any statistically significant clinical outcomes. Incidentally, the study got abandoned because the disease outbreak subsided in China. The subsequent Adaptive COVID-19 treatment trial documented significant benefit of Remdesivir in the subgroup who did not require high flow oxygen or any form of ventilation compared to those who were critically ill. Meanwhile, another randomized open-label trial by Goldman et al. documented no significant differences in clinical outcomes on the 14th day between a 5-and 10-day therapy duration of Remdesivir. Indeed, the adverse events were more (74%) in 10-day cohort compared to 5-day cohort (70%). Still, we need to mind the fact that many other trials related to COVID-19-related pharmacotherapy were abandoned due to failure of recruitment and many published evidence suffer the weaknesses of being an open-label compassionate trial, presence of confounding variables, unclear definition of lower respiratory involvement and ambiguous endpoints. Despite the fundamental uncertainty clouding around these drugs, the Government of India approved compassionate usage of Remdesivir in patients who are moderately ill and on oxygen as a 5-day intravenous administration. After that we could see the rocketing demand for this drug at hospitals and even at “black markets.”
How to mitigate these uncertainties? First, we need to accept the fact that these ambiguities/fundamental uncertainties which existed has become less in subsequent months when the pieces of the puzzle have been fitted. Secondly, we should be cognitively flexible while envisaging the evidence, try to search for more options/viewpoints and not succumbing to the emotional urgency induced by extrinsic sources. Taking cues from the epistemic belief model of learning by Hofer, knowledge can be viewed under four dimensions: simplicity, certainty, source, and justification. Though an evidence is a simple discrete fact obtained from an easy resource, reflecting based upon its certainty and justifying the credibility, would ensure the due weightage which has to be given. So, if we could rely upon evolving knowledge, check for the source of authorities transmitting, ascertain based upon its context and justify it in the form of critical appraisal, we could handle the ripples of uncertainty created by the hoaxes. Hence, the approach of the practitioners toward the evolving information should not be fact oriented and rather be pragmatic. Another option is conducting virtual reflective-collaborative appraisal forums where the collaborative knowledge building coupled with metacognitive reflection takes place. Pooling of evidence related to a particular drug and maintaining an active recurring folder would also be an optimal option. Therefore, the primordial duty of the practitioner is to eliminate the ambiguity, add the missing pieces to alleviate fundamental uncertainty by wilful gathering of data and pragmatically decide upon the management plan keeping in mind the basic doctrine of medical practice, i.e., “primum non nocere.”
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pieralli F, Vannucchi V, Olivotto I. The eighth alternative to evidence based medicine in the early era of the COVID-19 pandemic: Too much emergency and emotion, too little evidence. Eur J Intern Med 2020;77:163-4.
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailheet M, et al
. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949.
Hofmann B. The first casualty of an epidemic is evidence. J Eval Clin Pract 2020;26:1344-6.
Rochwerg B, Agarwal A, Zeng L, Leo YS, Appiah JA, Agoritsas T et al
. Remdesivir for severe covid-19: A clinical practice guideline. BMJ 2020;370:m2924.
Stirling A. Keep it complex. Nature 2010;468:1029-31.
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al
. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-78.
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalilet AC, et al
. Remdesivir for the treatment of COVID-19-Preliminary report. N Engl J Med 2020;383:1813-26.
Goldman JD, Lye DC, Hui DS, Marks KM, Bruno R, Montejano R, et al
. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med 2020;383:1827-37.
Baombe JP. BET 1: The role of remdesivir in COVID-19 infection. Emerg Med J 2020;37:522-3.
Hofer BK. Epistemic cognition as a psychological construct: Advancements and challenges. In: Greene JA, Sandoval WA, Bråten I, editors. Handbook of Epistemic Cognition. New York: Routledge; 2016. p. 31-50.