key: cord-0984877-4anmc7uc authors: Hofmann, Bjørn title: The first casualty of an epidemic is evidence date: 2020-07-22 journal: J Eval Clin Pract DOI: 10.1111/jep.13443 sha: 05c2ccee205faff533db6397b0821639b9794c7f doc_id: 984877 cord_uid: 4anmc7uc BACKGROUND: The COVID‐19 has posed a wide range of urgent questions: about the disease, testing, immunity, treatments, and outcomes. Extreme situations, such as pandemics, call for exceptional measures. However, this threatens the production and application of evidence. METHODS: This article applies standard categories in epistemology to analyse the pandemic in terms of four kinds of uncertainty: Risk, Fundamental uncertainty, Ignorance, and Ambiguity. RESULTS: Mapping the uncertainties of the pandemic onto the four types of uncertainty directs evidence production towards specific tasks in order to address the challenges of the pandemic: Eliminating ambiguity, being alert to the unknown, and gathering data to estimate risks are crucial to preserve evidence and save lives. CONCLUSION: In order to avoid fake facts and to provide sustainable solutions, we need to pay attention to the various kinds of uncertainty. Producing high‐quality evidence is the solution, not the problem. dence is the first casualty of an epidemic. We appear to be haunted by an invisible enemy, 2,3 and despite months with careful monitoring, extended testing, experimental treatment, and 18 702 scientific articles in PubMed (June 4), uncertainty still prevails. Our urgent need for information makes us lower the bar for evidence and thereby increasing the chance of bias and bad decisions. 4 The serious situation has led to ethical exceptionalism, 5 for example, in terms of controlled human infection studies. Correspondingly, we are exposed to an epistemic exceptionalism. 4 For example, the extremely rapid and "opinion-based" peer review 6 has resulted in a number of retractions of COVID-19 articles. 7 Accordingly, we seem to be subject to an "epidemic of false claims and potentially harmful actions." 6 In a situation with extensive uncertainty and an urgent need to act, understanding the character of uncertainty is key. The uncertainties of the COVID-19 pandemic can be mapped onto four types: Risk, Fundamental uncertainty, Ignorance, and Ambiguity. With Risk we have known outcomes and we know their probability distributions. With Fundamental uncertainty we know the outcomes, but not the probability distribution. When being ignorant we know neither. Ambiguity arises when experts disagree over the framing of possible contexts, options, outcomes, benefits, or harms. 8 Table 1 gives an overview of some specific and crucial uncertainties in the COVID-19 pandemic. Making decisions based on risks is not easy, but commonplace. The problem with COVID-19 is that so many risks are unknown, as probability distributions are wanting. Moreover, decisions based on fundamental uncertainty tend to be speculative and potentially harmful. 6 Decisions based on ambiguity "are not just potentially misleading they are a fundamental contradiction in terms." 8 Therefore it is crucial to clarify definitions. Additionally, ignorance poses great challenges, as we do not know what we do not know-and hence where to search for solutions. No doubt, scientists are working relentlessly to find answers to the many questions and solutions to the pandemic. But the desperate situation appears to excite desperate measures. 13 We are lead into what has been called a "once-in-a-century evidence fiasco." 14 In order to target our efforts to reduce uncertainty, we need to pay attention to the various kinds of uncertainty. Reducing risk 15 • This threatens the production and application of evidence. • This article directs evidence production towards four types of uncertainty in order to address the challenges of the pandemic. • The four types of uncertainty are Risk, Fundamental uncertainty, Ignorance, and Ambiguity. • Eliminating ambiguity, being alert to the unknown, and gathering data to estimate risks are crucial to preserve evidence and save lives. The first casualty of an epidemic is evidence. In extreme situations the imperative of action is strong. 16 This makes extreme measures tempting-including scientific and ethical shortcuts. 17, 18 Rigorous evidential and ethical criteria appear to obstruct progress. However, producing high quality evidence is the solution to the pandemic, not the problem. In order to avoid fake facts and to provide sustainable solutions science needs to pay attention to the various kinds of uncertainty. Eliminating ambiguity, being alert to the unknown, and gathering data to estimate risks are crucial to preserve evidence and save lives. I certify that there is no actual or potential conflict of interest in relation to this manuscript, and there are no financial arrangements or arrangements with respect to the content of this comment with any companies or organizations. I am the only author of this manuscript; The manuscript is sent exclusively to you, has not been previously published elsewhere, and is not currently under review elsewhere. Bjørn Hofmann https://orcid.org/0000-0001-6709-4265 COVID-19 and the anti-lessons of history Our Invisible Enemy The invisible enemy that will change the world forever Against pandemic research exceptionalism Biomedical research in times of emergency: lessons from history Coronavirus disease 2019: the harms of exaggerated information and non-evidence-based measures Keep it complex On the Importance of Early Testing Even when Imperfect in a Pandemic Such as COVID-19 Interpreting diagnostic tests for SARS-CoV-2 Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov) Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data Thinking of risk in the era of COVID-19 Optimizing the trade-off between learning and doing in a pandemic Research in disaster settings: a systematic qualitative review of ethical guidelines World Health Organization. Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies. World Health Organization How to cite this article: Hofmann B. The first casualty of an epidemic is evidence