Introduction
On December 31, 2019, a cluster of cases of pneumonia of unknown
etiology was reported in the city of Wuhan, China, and later identified
as being caused by a novel coronavirus. 1 The ability
of the novel Severe Acute Respiratory Syndrome CoronaVirus-2
(SARS-CoV-2; hereafter referred to as COVID-19)2 to
infect human hosts and be transmitted among individuals rapidly evolved
into a global outbreak with 2.2 million confirmed cases in 211 countries
as of April 17, 2020, 18:00 GMT-6
(https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
Though the majority (~80%) of the confirmed COVID-19
cases develop a mild condition, a smaller percentage
(~15%) of patients with confirmed COVID-19 require
hospitalization and some develop a severe condition
(~5%) that require mechanical ventilation in the first
24 hours of hospital admission.3 Clinical
complications such as profound acute hypoxemic respiratory failure and
sepsis requiring vasopressor treatment4, 5 have led to
a total number of 153,177 deaths worldwide
(https://www.who.int/emergencies/diseases/novel-coronavirus-2019;
last updated April 17, 2020, 18:00 GMT-6).
Worldwide, the capacity of the healthcare systems to offer care for
patients diagnosed with COVID-19 depends on ICU beds and emergency
departments (ED) capability to accommodate the additional care
requirements brought by the pandemic. This is of critical relevance
considering the high ICU occupancy commonly seen in many
locations6 and the long-recognized ED overcrowding and
its negative consequences on patient outcomes7-9.
Moreover, the current management of patients with COVID-19 is
supportive, and recovery time is estimated at around three to six weeks
for critically ill patients.10 In this challenging
scenario, it is not surprising that, following the recognition of
COVID-19 as a Public Health Emergency of International Concern on
January, 30, 2020,
(https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen),
there has been a frantic search for effective treatments. On April 6,
2020, there were 788 entries of COVID-19 trials registered on the World
Health Organization International Clinical Trials Registry Platform
(WHO-ICTRP), with more expected.
Clinical trials provide vital evidence to establish the efficacy and
safety of new medicines or new indications for existing medicines. To be
informative, however, they have to be designed and implemented with
appropriate standards to provide meaningful
evidence.11 Meaningful evidence fundamentally includes
the definition of outcomes that reflect efficacy/effectiveness
(beneficial treatment effect) and safety (effects of the treatment that
may be harmful to patients).12 Efficacy/effectiveness
outcomes should represent clinically meaningful results that directly
measure how a patient feels, functions, or survives.13Alternatively, trials may use surrogate outcomes instead of clinical
ones. Trials assessing surrogate outcomes may be completed faster and be
less expensive. However, surrogate outcomes may or may not predict
clinical results and translate in meaningful evidence of
efficacy/effectiveness.13, 14
Likewise, safety outcomes are essential in defining the value of a
treatment intervention for healthcare providers, patients, and health
systems. Despite the importance of finding a treatment that is effective
in mitigating or curing patients diagnosed with COVID-19, it is critical
to appropriately define and detect the potential adverse events of the
treatment options under investigation. There are guidance and legal
requirements for protocols of clinical trials to plan the data
collection of adverse events, whether applying systematic or
non-systematics assessment approaches 12, 15, 16. The
objective of this study was to assess whether the randomized clinical
trials (RCTs) registered on the WHO-ICTRP for patients diagnosed with
COVID-19 include definitions and data collection plans to produce
evidence on meaningful efficacy, effectiveness and safety outcomes.