TABLE 1.

Selected Quotations

Themes	Quotations
Responding to the critical and acute health crisis
Focus on saving lives	Right now the focus is keeping patients alive.
	There is one outcome that is far and away driving action and concern about this, and that is mortality. Everything else is secondary to the risk of death, for a self-limited acute disease where there is a substantial mortality. That is the major thing that we are trying to avert here, from the point of view of interventions. We are looking for interventions that will stop patients from dying. I would place mortality as out and away as a separate order of magnitude of importance.
	Mortality of course, because we see people dying, even young people without any comorbidity, they can end up on the ventilator and eventually die later on. We have several cases of young people, a very unfortunate one, a young girl of 12 yr who died in the ambulance to the hospital.
Preventing life-threatening complications	Right now the focus is keeping patients out of hospital, keeping them organ failure free out of the ICU and discharge home.
	Focus on the most severe end of the disease, these are problems that are going to, particularly mortality, multiple organ failure, sepsis, are clearly issues really for people who end up either in intensive care or who would go to intensive care were that to be an appropriate place for them to go.
	Multiple organ failure and the sepsis is a big one because I am one of the immunocompromised, I am in that high-risk category of COVID.
	Respiratory failure, multiple organ failure, sepsis are on the pathway to death unfortunately, and their significance is that that is what they lead to. Multiple organ failure is also important in my head because I do not know if he was going to then go into AKI because of COVID.
	It is very important respiratory failure because that is what everybody is so much afraid about to end up at the ICU and on the ventilator.
	It should be “severe” respiratory failure.
Capturing different settings of care
Minimizing burden on hospitals	Respiratory failure this position of the patients whether they are going to be cared for on the general ward, or whether they need admission into intensive care.
	There is the need to have outcomes that capture the hospital resources. Outcomes such as admission to hospital, admission to ICU, need for a ventilator to capture the different terms and labels of resources that we have in decent healthcare systems.
	We are trying to protect the healthcare system.
	The most relevant thing here is actually the need that patients will require mechanical ventilation, which can be actually one of the important core outcomes in patients. We have two separate basically two groups of patients with COVID. The patients who are treated in a normal ward. They are critical to certain extent until they need an ICU admission, and once the patients are admitted to the ICU, you will have a different situation actually with other outcomes of interests.
Recognizing events occurring in community contexts	We have 258 cases who died and 134 died outside of the hospital, mostly in aged care facilities. We were facing a bottleneck with the ability to admit patients and ventilate patients in ICU. A lot of people in aged care facility who were severely ill were not even admitted in hospital, because we knew that if they were admitted they would have required ICU which we could not offer to them.
	People who have suspected COVID-19 have the milder conditions would not necessarily end up at hospitals.
	I was in the hospital briefly, but not hospitalized per se. Multiple organ failure and sepsis were not an issue for me, but the shortness of breath, the breathing issues, I had a significant headache that I cannot begin to describe the severity of it.
	How much of these outcomes will be used in community studies as opposed to in hospital studies? My understanding is that COVID, certainly in the United Kingdom is absolutely prevalent in the community and we are not being tested so we do not know.
	I was at home for the duration of my illness. Luckily, I did not have it to a point where I needed to go to hospital or anything. My main thing was that I was so exhausted I could not move or do anything.
Ensuring relevance and feasibility in low resource regions	The options of ventilation and so on are restrictive. It is very relevant to realize that round about 87% of the world’s population actually live in low middle-income class countries. It literally has been a day and night job in our setting and for many of our friends elsewhere, and in fact on the continent of Africa… some of whom may not be able to in any context even offer ventilation—it is just not feasible.
	We are several weeks behind most of you, so launching the planning phases but we are seeing increasing numbers of patients and where ICU facilities do exist, and we are getting away in many instances the use of polymasks and proning a patient, without necessarily invasively ventilating them and patients who got saturation’s of 70% and 80%, where ordinarily in any other context these patients would have been invasively ventilated.
	The other thing that is really important is that we make sure that whatever definition we use is applicable across as wide a range of context as possible. So ECMO and something is very important in the developed world and so forth, but there are countries where ECMO is simply not available. In fact there are countries where even mechanical ventilation is not available. So we must make sure I think that this is as applicable across contexts as we can manage whilst not collapsing things of saying advanced respiratory support is all the same, but also to try and capture from as many contexts as possible so that trials do take place in less well resourced areas can also take part in the core outcome set.
	I am speaking on behalf of the low- and middle-income countries. We have seen a lot of patients with multiple organ failure because these patients arrived late in the hospital because sometimes they are stuck in the other parts of the national healthcare system. Multiple organ failure will be an important issue in this scenario.
Encompassing the full trajectory and severity of disease
Addressing prognostic uncertainty and long-term concerns	The most important thing to me would not be if I died with COVID, it is just if I got it and was worse and it destroyed say half my lung function or to quality of life.
	It is about ability to function afterwards. I have no comorbidities to my knowledge, but what is worrying me now is post viral fatigue and recovery, because it is been a very long time since I’ve spent 2 wk in bed, and I am showing no signs of being strong enough to even function in the house, never mind go back to work. What is concerning me about a long-term recovery is that kind of post viral thing, and then also are there lung injuries for people that do not even have comorbidities? Am I at risk of suffering some term loss of some lung function?
	I am at day 26 now of having the disease, and I still have a fever, and I still have a really high heart rate, and I still have shortness of breath and chest pain and a cough. I am grateful that I am not in hospital with more dire symptoms. I am a musician and I use my lungs for a lot of things. The long-term effects of the disease would be something good to look at.
	In terms of fatigue, I am a very active person and I cannot stand for more than 10 min anymore, and that is a really weird feeling in my 20s. I am really scared when they do tell me that I can go and get an x-ray, what my lungs are going to show because I have never had that kind of chest pain and shortness of breath before.
	I had side respiratory failure and I would like to make a pitch for some long-term consequence of COVID-19 infection being included in the core outcome, such as pulmonary fibrosis. Because you could imagine a kind of discreet choice experiment, where a clinician or a patient or a health provider has to decide, “Do we ventilate harder to get the patient off the ventilator sooner, but risk more pulmonary fibrosis long-term?”
Applicable to mild and moderate disease	I treated about 30 patients with COVID-19, some mild patient, some mild disease. They were hospitalized on a standard floor, so they were treated with first some oxygen by the nasal prongs.
	There will be a period of recovery. This week I can have a shower and go downstairs and have breakfast and I am not short of breath, whereas last week I could not do that. So that is an indicator of some measure of recovery.
	Shortness of breath can be a good outcome parameter in the sub pool of patients who are admitted to normal ward, not patients in ICU.
	Fatigue, shortness of breath are very important from patient perspective especially in patients who have milder form of disease.
	Absence of disease [recovery], which surely is one of the outcomes that one is trying to accomplish when one is conducting a trial is to cure people and to get rid of the disease.
Distinguishing overlap, correlation, and collinearity
Symptoms having distinct value	Shortness of breath was one that was quite debilitating for me, in terms of trying to do some normal things like washing, like cloth washing or tidying the flat, I had get very short of breath. It was the shortness of breath and the fatigue that lasted the longest, and it was at that stage when I did not have the fever or anything else. How long until these symptoms go so I can get back to a level of normality in life, and go back to work, do gentle exercise?
	The issue with shortness of breath is, it is not very specific but that may be a good thing, because it is more sensitive in that regard.
	Shortness of breath is strongly related to ICU-acquired weakness.
	We should be including shortness of breath to capture that patient experience.
	I consider myself somebody who has got a moderate case. I have been dealing with this almost 4 wk now and I am still having shortness of breath and other symptoms. It is troublesome not to be able to breathe.
	Even though I do not have the virus in my body, I am still having shortness of breath, chest tightness, and I am still coughing as well.
	Shortness of breath maybe important in self isolated patients at home, usually a chest radiograph cannot detect the pneumonia in COVID-19. Some of these patients who have shortness of breath, can, progress quickly to the respiratory failure, so the shortness of breath maybe can be the only sign of the respiratory failure or pneumonia.
	There are ICU data showing that shortness of breath, even a patient on a ventilator has some prognostic significance. So shortness of breath seems to be different from respiratory failure and [the patient’s] comments about her father having respiratory failure but not being short of breath, quite pertinent. I think it matters to the person about how they feel. And so I would favor including shortness of breath.
Clarifying causal pathways	There is a major overlap between multi organ failure and sepsis, particularly with the definition change in sepsis, where organ failure is vital to that. Those are really the same thing because this is drive by an infection so therefore by definition any multi organ failure arising from COVID is sepsis.
	If we are going to combine them to delete the sepsis terminology. Sepsis is a very vague condition.
	Multiple organ failure is a bit tenuous but it is important, we have seen a lot of kidney damage, a lot of AKI, a lot of need for dialysis and it seems to be effecting outcomes or how well or how poorly they are going to do.
	I have been rounding for almost 4 wk now in a row, is very variable if the patients are going to go into multiple organ failure or not. The one that I have in the unit, obviously they have more chance of having multiple organ failure.
	Multiple organ failure and sepsis was somewhere on the causal pathway between the respiratory failure and mortality.
	Most of the cases that we saw so far in our institution, they died not only from the respiratory failure, they died actually from non-respiratory organ failure. So non-respiratory organ failure can also be an important outcome parameter in these patients, mostly coagulation failure.
Recognizing adverse events
	There is a lot of studies that are being started that are evaluating hydroxychloroquine for example, which has adverse events. So especially the population of patients who are not as severe, so instituting this treatment can be problematic and can institute adverse events.
	Adverse events are often intervention specific and so they are not going to have a common domain across all different drug classes or other intervention foci in an area here where there does not seem to be any compelling cases or effective interventions at present, that just adds to the uncertainty.
	A topic that is of relevance is also the harms, the side effects. We are potentially going to be trialling a lot of novel interventions. The question is, what is the trade-off between the potential benefits, the respiratory failure, whatever, and those harms which probably we are going to have to accept to obtain certain benefits.
	We should be aware of the variation in approach to treatment around the world and the way that that is evolving quite rapidly. Outcomes that are more based on physiologic state rather than the initiation of a particular therapeutic intervention may be a better approach.
	Being cognizant of family and psychosocial wellbeing
	The impact on family is quite huge to have those social issues to be looked at as well, considering when we are talking about people isolated in hospitals and do not have any contact with their family and how difficult that is and how stressful that is and could actually equate to you actually being sicker and deteriorating a lot quickly into depression and anxiety. We have seen people over on social media where they have had to stand outside and speak to their loved one on a walkie talkie to say goodbye because they are dying.
	It is still depression to me or psychologic issues associated with the disease is still a very big thing, both for the family member. I was actually out of hospital before my father was, and I gave it to my father. I did not fall into depression, but I can actually see how people will have a lot of anxiety about passing it to their family members and also that they may go into depression.
	Are we picking up anything on psychologic wellbeing or worry, anxiety, sense of control.
	And then the last thing specific to the safety net population is this idea or this outcome of vitality and financial stability. I had several patients that actually left against medical advice, so still requiring oxygen and hospitalization, but left because they thought they needed to go back to work and there was nothing our hospital could do to keep them there in the hospital or to let their employer know that they were infected, but they had to go back to work because they were day laborers and needed to make an income for their family.
	I was worried about whether I had given it to anybody when I went to the doctors. I was just constantly worried and I do not feel like anybody’s talking about the anxiety side of what having coronavirus does.

AKI = acute kidney injury, COVID = coronavirus disease, ECMO = extracorporeal membrane oxygenation.