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[00:00:07] Angela: Hello and welcome back to Communicable, the podcast brought to you by CMI communications ESCMID's open Access journal, covering infectious diseases and clinical microbiology. My name is Angela Huttner. I'm an infectious disease doctor at the Geneva University Hospital in Switzerland, and editor in chief of CMI Comms.

I'm excited today to introduce two guests for a discussion on ethics in infectious diseases. The first is Dr. Zeb Jamrozik, a general physician and bioethicist whose work focuses on philosophical and policy issues related to infectious diseases and global health. He completed his PhD at Monash University in Melbourne, Australia.

His doctoral thesis covered some of the ID ethics issues we grapple with from day to day. Those related to asymptomatic infection, antimicrobial resistance, vector-borne diseases, and some that may be more esoteric to some listeners. The ethics of Human Challenge studies and other types of ID research.

Zeb worked for several years at the University of Oxford on infectious disease ethics and has contributed to multiple World Health Organization's ethics guidance documents. Most recently on wastewater surveillance, he returned to Australia to continue clinical work and bioethics research, and is now a member of ESCMID's Ethics Advisory Panel.

[00:01:25] Angela: Zeb, welcome to Communicable.

[00:01:28] Euzebiusz: Thanks, Angela. It's great to be here.

The second guest is Dr. Beenish Syed. Beenish is a consultant in infectious diseases and assistant professor of infectious diseases at the Dow University Hospital, Dow University of Health Sciences in Karachi, Pakistan.

Her research interests include COVID-19 multi-drug resistant organisms, and HIV. She serves on the infection control and antimicrobial stewardship committees at her institution, as well as the ethics advisory Committee of the transplant unit. like Zeb she's currently a member of ESCMID's ethics advisory panel.

[00:02:04] Angela: Beenish, welcome to Communicable.

Beenish: Thank you.

Angela: So, as our listeners know, we always start with a get to know you question. Some of our guests tell us that it is the hardest question they're faced with. This one is easy though,

[00:02:17] Angela: What is your most used emoji? mine actually depends on who I'm writing, because if it's anybody in my family or my friends, it's the awful cat emoji with the heart eyes. However, if it's work, I tone it down and I just do the smiley, which is bland, but hopefully says what it needs to say Beenish

Beenish: While I'm at work, the thumbs up emoji. I think that's the emoji I mostly use while in my family and friends, I think it's just smiling emoji. Or the hard one for my nieces and nephews. Yeah.

[00:02:51] Angela: Thumbs up. Super practical. So glad they invented that one. you zev. What's your.

[00:02:56] Euzebiusz: Well, yeah, like everyone else, I guess I'm using the thumbs up, smiley and, thanks emoji the most. But if you exclude those ones, I guess one of the ones I like is, the flame emoji because you know, when someone just says something, it's just so perfect.

[00:03:09] Euzebiusz: It's like they're on fire, I like that in a text message conversation. Yeah.

Highly expressive. Yeah, totally. I think emojis are like one of the best inventions ever. So, to our discussion, which is unfortunately not as light and, happy as emojis.

ethics in Id, infectious diseases in particular because I do think our field of medicine is different. infectious diseases is in a world apart. I tell my medical students actually that we ID and clinical microbiology people, we've got this sort of added complexity. A certain tension. We have the patient in front of us that we need to treat, that we can't fail. But behind that patient, we've got all these invisible patients that most other people cannot see, but they are there. They are the patients of tomorrow, some of them literally tomorrow with antimicrobial resistance.

[00:04:03] Angela: When we make one decision to treat. With one antibiotic. Antibiotics being a non-renewable resource, we're not really deciding for one patient. There will be effects on many other patients. And I always knew from the beginning that there was this tension. We all know this, but it hasn't gotten more subtle or more manageable over time.

[00:04:22] Angela: I'd say it's only grown and of course it's there all the time in public health where we will also have limited and or non-renewable resources and in clinical research too. And there we're not unique from other physicians or healthcare professionals. It's the same tension, the individual versus the group.

[00:04:40] Angela: What are the rights of one versus the rights of the other. So my first question is for you Zeb, what makes antimicrobials different from other scarce resources? And what framework do you believe is most ethically appropriate for allocation of these limited resources?

[00:04:58] Euzebiusz: Yeah. Thanks Angela. that's a great question.

[00:04:59] Euzebiusz: I think it really gets to, you know, what's different about infectious disease and what makes for some of the most, interesting, kind of ethical tensions. Other types of scarce resources that people have thought more about. Things like ICU beds, there's well established frameworks if we have a crisis and there's not enough ICU beds, not everyone agrees, but people can argue about which factors could be relevant.

Is the age of the patient irrelevant consideration? Is there level of comorbidity or their likelihood of survival relevant? And how much weight should we give to each of those considerations to decide who gets the limited resource? But antibiotics are quite different in a few ways. aren't they? You know, if we think about just, antibiotics specifically rather than antivirals and antifungals, which might be slightly different, Like you mentioned, it's a scarce resource, but it's a different type of scarce resource to ICU beds. and that's for a couple of reasons. one is that there's gradually increasing antimicrobial resistance over time, and that's partly due to use of antibiotics and partly due to transmission or prevalence of resistance in the community.

[00:06:02] Euzebiusz: and I guess one of the key things is this question about transmission. if the individual clinician is deciding about how to use antibiotics in their patient, an important question is, well, what are the chances that that person not only will get harmed themselves, but transmit resistance to others?

[00:06:16] Euzebiusz: And you know, it depends on the setting that you're in. because, it doesn't look like clinical use of antibiotics is necessarily the main driver of the prevalence of resistance at the population level. so for example, at the global level, high income countries have used more antibiotics per capita for years, but have a much lower prevalence of antibiotic resistance.

[00:06:38] Euzebiusz: whereas low income countries, which even if you account for over-the-counter sales overall use less antibiotics per capita, but have a quite a high carriage rate of resistant gram negatives, for example. And that tells you that clinical use isn't the only consideration. There's always considerations about, what happens out there in the environment.

the other thing to keep in mind is that questions have a level of the individual, antibiotics are not a renewable resource, but there is at least some renewal of sensitive bacteria. Like we know that people, if they get colonized with resistant organisms, in one year's time, if they haven't been exposed to more antibiotics or other sources of resistance, actually the sensitive organisms take over.

[00:07:16] Euzebiusz: And, so it is renewable in some sense, and in the total population in nature, there might be more renewal than we think provided that the selection pressure, exposed by antibiotics, is taken away. but that's a long introduction. Yeah,

[00:07:29] Angela: you're bringing up a couple of really interesting points.

[00:07:32] Angela: first of all, I of course agree with you that. antibiotic targets so the organisms can become more susceptible over time. Right. that's been well documented, but the way that that happens is that you remove the antibiotic use, right? You remove this selection pressure. And the question is, who has time for that?

[00:07:51] Angela: Right? I mean, like, you're not always in a setting where, we can wait for those bacteria to return to wild type, you know? and it's just not happening in some countries. Maybe Beenish wants to chime in there, but, , I agree that on, this, grand scale on a very theoretical level, These are renewable if you wait around long enough and if you hold back in their use, which is a really difficult proposition,

what I have experienced here is that, we are already low on the newer antimicrobials. the stock of anti-microbials and the newer anti-microbials that are active against the multi-drug resistant organisms. Already in Pakistan we don't have the combinations of beta lactam and betalactamase inhibitors, for instance, fourth generation cefiderocol, which covers all the organisms. Gram-negative, gram positive. This becomes even more difficult for us, because we don't have those antibiotics to support us.

We start seeing colistin resistant organisms now. So much carbapenem resistance. And on top of that, we are so overwhelmed by the number of, patients in the intensive care and same. the shortage of staff, especially in the ICUs and the critical care units because, the patient who has, has multi-drug resistant organism. What is generally recommended is having a one to one nursing, right?

[00:09:11] Beenish: So in our setups, we do not usually get that. There's one single nurse who's caring for about three to four patients. So what is happening here is that transmission is becoming so easy, we do not have the time we do not have that luxury that we. isolate that patient and, apply the full, force of infection prevention and control to limit the spread of those organisms. for us, it becomes, problematic on so many levels.

we don't have the antibiotics and the infection control to implement Those practices is also a challenge for us. And then we do have stewardship in our hospital because it's a large hospital. It's, connected to a university. And there are other bigger hospitals in, especially in Karachi, that Have these, antimicrobial stewardship programs, which do help in some way.

[00:09:57] Beenish: we were able to, implement a policy in [00:10:00] our hospital for restricted antibiotics when you need to prescribe a certain antibiotic, you have to have the ID input for that. So in that way, we're trying to curtail it, but it's, very difficult.

we do not have these organisms so much in the community, as for now, but we do have the resistance in the, community in the form that our animals are being fed those, broadspectrum of antibiotics.

[00:10:23] Angela: thanks Beenish, and I think you've made some points Beenish that also, kind of illuminate this sort of crazy paradox that Zeb Has mentioned that in high income countries, which use the most antibiotics, we see relatively lower transmission.

[00:10:40] Angela: And I think it's like you say Beenish, because those countries have , the means to, isolate patients and control that actual transmission it's always a two step event, right? That they can give the antibiotic, but then they can break off the chain right there.

[00:10:54] Euzebiusz: I think it's good. you've highlighted that we need to separate the ethical tensions that arise in the context of transmission. So we've already talked about this question of infection control, preventing transmission between patients and so on. That's one set of ethical tensions from the ethical tension about prescribing.

[00:11:11] Euzebiusz: The risk that your patient is gonna transmit resistance from another person is actually smaller than most people think. depending on the, setting. And it can be controlled in other ways. That's beyond the individual prescriber. But I think the real. Key ethical tension for prescribers is a very basic one, which is the trade off between benefits and harms.

[00:11:29] Euzebiusz: with each prescription of antibiotics, we want to maximize benefits and minimize harms and primarily thinking about this particular patient. And I think the biggest ethical problem is antibiotic overuse. And that clinicians don't think enough about the harms and overestimate the benefits,

[00:11:46] Beenish: Exactly. Yeah.

I'm a real fan of this movement. shorter is better. for years we've been telling patients, you know, moralizing with patients, you must finish the course of antibiotics. You must take the long courses of antibiotics. And it turns out that's not true, that most people with uncomplicated infections probably get better after one, two, or three days of antibiotics.

[00:12:06] Euzebiusz: We don't even know what the shortest possible course is, you know, but each time they do a trial looking at shorter courses, the shorter courses look like they're just as good as the longer courses. And that suggests that if we wanna maximize benefits and minimize the harms of resistance, as well as antibiotic side effects, we need to be treating with much shorter courses on average than we are now.

[00:12:25] Euzebiusz: because we know doctors often exceed the guidelines and the guidelines often exceed the research. And so I think a lot of, antibiotic prescriptions. More harmful and less beneficial than we think. I know that's a controversial thing to say.

[00:12:37] Angela: I think all infectious disease people do agree, especially stewards.

we are very much in agreement and the question becomes how do we convince our colleagues that. the individual patient in front of you might fail. you may take it as a personal failure that your patient had a treatment failure, but this could happen even if you give that patient, two weeks of antibiotics versus one.

[00:12:59] Angela: Guess what? Two weeks after stopping the antibiotic, it may well be the same result. how do you assure your colleagues that when it's all theoretical, they can't, know. do we need to change the culture? I struggle with this in my own service.

you really sometimes feel, ah, but if you stop too quickly, you're being cavalier, right? You're being, careless with an individual who's very concretely in front of you, That's where people see risk. They don't see it in the future. Patients who are coming tomorrow

[00:13:29] Euzebiusz: or in the harms for that particular patient who, you know, in one month's time is gonna come back with resistance because you gave them two weeks of drugs and you're selecting out the resistant organisms in their bowel, and that makes it more likely that they're gonna have resistance in future.

[00:13:41] Euzebiusz: We just don't see that enough. And like you say, we've been using ethical language. We say people have bad doctors if they don't give enough treatment. Patients are bad patients if they don't take enough days of medication. But turns out, that's upside down, you know? And we need to totally reverse that language, I think, in a lot of cases, especially for uncomplicated bacterial infection.

[00:14:01] Angela: yeah. I think We are all very much aligned. I have a question for Beenish. Sticking with scarcity of resources, do you think that it's ethical to prioritize healthcare workers for access to limited treatments or vaccines? not necessarily antibiotics, moving to any kind of treatment, vaccines as we just experienced in COVID.

I also drive my experience from the pandemic. the vaccines arrived really late in our part of the, world, . So the first people who were vaccinated were the healthcare workers. They were given the priority in the first month, all the healthcare workers.

[00:14:36] Beenish: And it was mandatory. There was a mandate that everyone has to be vaccinated I believe, that this, was good in a way because of the amount patients we were seeing at that time before the vaccination.

[00:14:48] Beenish: we needed those healthcare workers to be safe and Be there for those patients. And because, there were lockdowns and there were restrictions the . only, bridge between the general population and the infected patients especially immunocompromised ones or the were the doctors, right?

[00:15:04] Beenish: when you, prioritize and you vaccinate those, healthcare workers first, the numbers actually started to come down gradually and the severity of the disease also came down.

WHO also recommends that the flu vaccine should also be given to the healthcare workers first. I have read this in a research article. I think it was published in The Lancet. Was it was a application, based on ethics.

[00:15:26] Angela: I should have reframed that question I should have turned it on its head and said. How is it not ethical to prioritize healthcare workers for access to limited treatments or vaccines?

[00:15:37] Angela: Right. Is there an argument against it? It seems fairly straightforward, but perhaps there is some other approach.

[00:15:45] Beenish: you know what, I actually have an example two Nordic countries at the start of the pandemic, when the vaccines rolled out, they actually did not prioritize their healthcare workers, and they, uh, chose to vaccinate the, elderly people who were more at risk of giving the COVID vaccine.

[00:15:59] Beenish: later on, they had to reverse that decision and vaccinate their healthcare workers first. Because they're the first responders, the first line workers, Even though, it's come from a personal perspective as well, I've been there even if it's the other, resources, not just the COVID vaccine.

[00:16:15] Beenish: I think it, comes, down to being, ethical that the healthcare workers, be prioritize for limited resources,

Zeb, what do you think?

[00:16:22] Euzebiusz: Well, most people agree that in a epidemic emergency healthcare workers should be prioritized for limited resources like vaccines, but also ICU beds if they get sick.

[00:16:33] Euzebiusz: but the really difficult ethical question is how much priority should we give to healthcare workers? Because healthcare workers face additional risks. and because society has a self-interested reason to keep healthcare workers alive so that they can look after other people, we should give them some priority.

[00:16:48] Euzebiusz: the question is, how much priority to give them? Because there might be situations where if you give too much priority, well, other people could lose their lives. for example, like Beenish said, if you give the healthcare workers vaccines rather than people at higher risk of the epidemic disease, then some of those people might die.

[00:17:06] Euzebiusz: Or if you give healthcare workers priority, say a 50-year-old healthcare worker, you prioritize them for ICU because they have COVID-19. Well then a younger person. who's not a healthcare worker might not get an ICU bed. so it can have consequences. my view on this is that there needs to be a conversation in each society about how much priority we give.

[00:17:24] Euzebiusz: it makes sense to give some priority but not absolute priority. There might be situations in which other people's interests, matter more when the healthcare workers, but in general, at least some priority needs to be accorded.

so along the lines of COVID, we've been through a crazy times of, in the last few years with this pandemic.

[00:17:42] Angela: Many governments imposed essentially coercive public health measures like lockdowns. These are not new ideas, but for those living on the planet in 2020, they were completely new. We saw real costs on many levels. So what would you say is the ethical justification for coercive public health measures like lockdowns, quarantine?

[00:18:00] Angela: Where should the limits be?

[00:18:02] Euzebiusz: It's obviously a very big, controversial area, and a key word, that you use. There is coercive measures, the kinds of measures where we use the full force of public health law and we use police and sometimes military to enforce public health orders.

[00:18:17] Euzebiusz: That's what makes it a coercive measure when there's very negative consequences for people who are gonna break the rules and whether it's enforced by police. you know, this word lockdown, you might know it originally comes from prison management. When there's a riot in prisons, they lock down the prison, they lock prisoners in their individual cells, to calm down the prison.

[00:18:35] Euzebiusz: so it's not necessarily the kind of approach that many people think should be or has been associated with public health, which is often about trying to understand people, communicate with them, try and achieve population health without forcing people to do things. and I guess one of the key limits, is how much harm.

[00:18:55] Euzebiusz: Those measures and those coercive enforcement strategies are gonna cause. we have some ethical frameworks, ethical principles in public health ethics to define the limits of, this. And one of the key, principles is proportionality. So the idea is that, we should only use so much force or coercion, so that, so that our measures are proportionate.

In other words, that the. Benefits of the intervention outweigh the harms. when it came to lockdowns, maybe early in the pandemic, it looked like the benefits were going to outweigh the harms for a short period of time. But as those measures carry on for long periods of time, the harms accumulate and the benefits go down.

[00:19:34] Euzebiusz: so that's one limit is once the harms start to outweigh the benefits, we should stop. and the second limit is more based in justice. So if, a lot of the benefits of an intervention are going to, relatively wealthy advantaged people, like the kind of people who can work from home, and, a lot of the harms are going to disadvantage people, or for example, children when it comes to school closures and that benefits and harms aren't being fairly distributed in society.

[00:19:59] Euzebiusz: And I [00:20:00] think we saw that with lockdowns. Well, that's another reason to rethink those measures if the harms are occurring to disadvantage people or children. I'm hopeful that in the next pandemic actually we'll be using less coercive measures, and, relying more on a, cooperative approach between public health agencies and populations.

[00:20:18] Beenish: What we saw in Pakistan, what it was like dealing with the lockdown and the implications it had on the general population here, considering about 44% of our population lives below poverty. if they do not go out, and not, do whatever they do to, earn a living, then they will go hungry. When initially when the government imposed, lockdown, people were being provided, , with rations and with food and stuff, but that was on a very limited level, Because the population we have, 50 million people, So it's not possible for the government to provide, such large scale assistance. when that started to show, its negative consequences, especially for these day-to-day workers. The working class were very severely affected with a complete and total lockdown. we saw negative implications of that in India, right the next door So there was like utter and total, devastation to The working class over there. And same thing happened in Pakistan. the coercive measures, the reality of the situation is different, for the higher income countries and for the lower income countries, it's very stark. for us, coercive measures. affects

[00:21:22] Beenish: The individuals their individual rights, but it also, adversely affects their economic situation, and their finances. for these coercive measures to take effect in lower companies, you have to take all these things in mind.

[00:21:35] Angela: Yeah, I think we'll be. Parsing this whole COVID pandemic nightmare for many years to come. But in my humble opinion, we humans were so much less, adaptive than the virus.

[00:21:47] Angela: You know, we were very, rigid and we kept trying to apply, measures that were understandable for the first wave. But I think some governments just didn't get it. things were changing. Both inside the virus and out, let's say. Yes. hopefully next time around we'll be more adaptive ourselves.

Anyway, Beenish, I have another question for you, not necessarily related to COVID. How do you think clinicians should respond when patients refuse infection control measures in hospital settings?

[00:22:19] Beenish: it's an interesting question from my perspective, I've been working as an infectious disease clinician for the past 7 years now, and practicing infection control very actively.

[00:22:30] Beenish: So I don't think the patients pose that much of a problem in Pakistan but if they do, what we have to do essentially is educate them. The problem with us here is We lack the resources. I work in a, non, profit organization, and it charges.

[00:22:46] Beenish: Its patient for the, services it provides, but there's no profit from it. We have ample resources available to us. But even then, it's not easy to allocate them and utilize, the supply. It's not adequate even with a private organization. But when we come to the public sector hospitals, it's essentially non-existent. The resources that we need for the infection control practices, Like hand or even source with water, proper sink, masks.

[00:23:13] Beenish: For the patients and for isolation rooms, there are essentially no isolation rooms available, it all boils down to the resources rather than our patients being compliant for our patients. We only have to just talk to them. generally the large number of our population unfortunately, lack education, it's not easier to make them understand. But what we have to do on our part is that, talk to them in their language, what is easier for them to understand and make things easier for them, right.

[00:23:43] Beenish: Like, what is the minimum that can, that can be followed in their situation, So I think it's not that difficult. what we have to do improvise in the situation, whatever the situation is, education is important and, talking to them in their own terms keeping in mind their beliefs, their cultural beliefs, that is also very important.

that makes a huge part of the conversation in our world the cultural values religious values, so they all come into play

fantastic answer you're essentially advocating education, listening to the patient, and I don't hear any, hint that, well, sorry, you know, society's gotta win, patient has to be forced, et cetera, et cetera.

[00:24:20] Angela: That has not been in your toolkit

at some point they do. They actually do. have to restrict. Right. but that comes later when they actually do not wanna listen. then you have to force. But before that comes education because We have to understand where they're coming from. See, they do lack the resources. They do not have the basis of the education that we have.

[00:24:39] Angela: Yeah. Yeah.

[00:24:39] Angela: Zeeb, what about you? any thoughts, anything to add on that?

[00:24:43] Euzebiusz: a lot of our infection control measures aren't very evidence-based. and so it would be nice if we could do more research looking at, well, what is the most effective intervention?

[00:24:55] Euzebiusz: Are all of these measures actually necessary and so on, because. You know, in some places in the world we're starting to use less, for example, gloves, less gowns, which were previously perceived to be necessary and now maybe aren't so necessary in certain circumstances. So I think before we, you know, have restrictive policies, it's good to have evidence that they actually produce a benefit.

[00:25:16] Euzebiusz: but like Benish said, I guess the. place where the biggest tension is and where there's a limit is the question, does the patient pose significant risks to others? And if they don't pose significant risks, well then, there's not so much of a problem. But the situation where they do pose significant risks can be much more challenging.

[00:25:32] Angela: Thank you.

so Zeb, along these lines, in 2023, you co-wrote an opinion piece entitled The Ethical Obligation for Research During Public Health Emergencies Insights from the COVID-19 Pandemic, in which you argue that high quality research, namely by means of well-designed, randomized trials,, is ethically obligatory before, during, and after implementation policies in public health emergencies in the world right now.

[00:25:59] Angela: These countries are pulling out of WHO and other international bodies, how do you see this happening? Do you think individual patients will agree?

Yeah, thanks. Great question. and yeah, I'm a big fan of research and evidence-based public health practice. a lot of people think The job of research ethics is finding problems with research.

but what I wanted to highlight in that piece is that sometimes there's a strong ethical case for research. You know, as long as it's appropriately designed and so on. and one reason there can be a strong ethical case is because we really need to know. In a public health emergency, what effect our interventions are having?

[00:26:34] Euzebiusz: how big are the benefits? How big are the harms? How are those benefits and harms distributed? sometimes we need more than just public health surveillance. We need research to help to answer those questions in a really rigorous way. and in that paper you mentioned, we try and explain why there's a strong ethical obligation.

Well-designed research. There's a strong ethical case to do that during emergencies. And the reason is because we really need to know in an emergency, what are the outcomes of our interventions? what benefits are they causing?

[00:27:01] Euzebiusz: What harms are they causing, and how are those benefits and harms spread in the population? And some people have. Different views on this. Objections to that. They say, we don't have time for research. It's too urgent. Or they say, we should use the precautionary principle. We should just assume that the interventions work.

[00:27:17] Euzebiusz: just like we assume that parachutes work and we shouldn't take the time to test, those interventions in, you know, proper randomized trials. But the problem is that if we do that, some of our interventions turn out to have no benefits, or very minimal benefits. Some of them turn out to have significant harms.

[00:27:34] Euzebiusz: I think we saw in the COVID pandemic lots of examples of interventions that were brought in based on very weak data and eventually abandoned, for one of those two reasons. And I think some of the real positive news from the COVID-19 pandemic was the research successes, the things that brought us, you know, even simple interventions like Dexamethasone for example, for hypoxic.

[00:27:54] Euzebiusz: COVID-19 was based on a high quality trial. and I think we need more of those trials, not less. In emergencies

[00:28:01] Angela: Yes, that was, the framework of the COVID-19 pandemic. But, This question remains even for regular research, just advancing medicine, advancing, our knowledge and our ability to treat patients. I think the central tension between the individual and the group. What are the rights of each, which one should, Sort of, win out. What about cluster randomized trials? Right? Where You need to randomize the group and everyone in that group should be participating right the way it is.

[00:28:31] Angela: I know the Netherlands does a lot of cluster randomized trials. They are allowed to. Randomized, the entire group, let's say a hospital unit, hospital, ICU, but

[00:28:39] Angela: after that randomization, they need to get their consent.

[00:28:43] Angela: And if the patient doesn't give that consent, and understandably, that patient may not want to, having just woken up and learned of all these things that actually happened while he or she was sleeping. Those data can't be used. So that entire research project, which includes putting that patient, into a randomized scheme without his or her consent, all of that is, wasted.

obviously not entirely wasted. There should be enough data to, come out with something, but it will be biased. how do you feel , About ethics committees adopting, the idea of opt out consent. By families, of course, if necessary by proxies.

[00:29:20] Angela: A lot of countries have proxies. But, essentially creating a framework where you don't put the onus entirely on the patient to give, so-called informed consent, which by the way, I have, lots of opinions on what informed consent really is. Great. really interesting issues to unpack there.

I guess one of the first things, to remember is that informed consent is, not the only ethical protection for research, right. you know, peer review of scientific protocols is a form of ethical protection research. Ethics committee review is a form of protection, community engagement about what type of research is permissible under what circumstances.

[00:29:59] Euzebiusz: That's a form [00:30:00] of protection. Individual informed consent is, important, especially for certain types of research, individual clinical research. but it's not the only ethical protection. And so I think at least in some countries, there is a move towards a model where low risk research could be done under certain circumstances without necessarily relying on traditional informed consent.

[00:30:20] Euzebiusz: And I think one ethical reason for that. is that, patients are already effectively randomized when they turn up to a hospital because which hospital you go to, which clinician you get admitted under and so on, can result in different treatment strategies. It's randomization of care, but it's not randomization in the research sense.

[00:30:39] Euzebiusz: Overall, that's probably bad for patients, right? Because, in the long term we don't know whether some patients are doing better than others because we're not measuring it in a rigorous way. We're not randomizing them, properly. you raised a really interesting point, about bias.

[00:30:52] Euzebiusz: Right. So, we need to do rigorous research where people are properly randomized rather than just going under a different clinician, because there's all kinds of factors that might bias the outcome. So one approach, like you mentioned, would be to do a cluster randomized trial where we allocate, people, to an intervention or not.

then there's this question about, well, should we retrospectively seek consent from those individuals? So some institutions say, well. By coming into this institution, you agree to having certain types of low risk research done on you. , In that situation, if you are only being randomized to treatments that are accepted by many doctors in the hospital anyway, it doesn't seem like the risk of being randomized in that situation is very high. So maybe that's ethically acceptable to do that.

kind of prospective waiver of involvement in research. another approach can be, like you mentioned retrospectively seeking individual consent, but that can be quite difficult to do. To what extent does that bias the outcome?

most of the time probably it won't. prevent us from doing the trial If 5% of people opt out, that doesn't necessarily cause the trial to fail. But a key question is, does it bias the outcome? And you might imagine there could be a model where, when people opt out, well, maybe their data are retained just for a check of bias.

Like, was the de-identified data set of people who opted out. Different to the people who didn't opt out because provided there's no systematic difference between the people who did and didn't opt out well, then it won't necessarily bias the data, but it certainly will reduce the sample size, and might require, you know, larger studies and so on.

[00:32:22] Euzebiusz: In any case, it's very labor intensive and it's probably not the best model. Ideally, we would move towards models where low risk research randomizing people to widely accepted interventions to try and learn more about what's the best approach maybe that can be done with different models of ethical oversight and consent than the ones we've used to date.

I think that's an exciting area for innovation, in research ethics.

[00:32:46] Angela: I fully agree and I, look forward to that day. but I think there is always this question of, wait a minute, what about the individual patient's Right. To keep that, his or her own data private.

[00:32:57] Angela: I feel like right now we're in this. Time period where , the right to privacy data is extremely important. And that almost trumps the group and the group's rights to better science, better medicine.

[00:33:10] Angela: how do you deal with that? There are various reasons why it's important to maintain some capacity to opt out of research, or, you know, the right to withdraw from research. One reason is because, a lot of research is very low quality research and, there shouldn't be an obligation to participate in that.

another reason where the right to withdraw is very important is where there's lots of risks in research, but lower risk. research, that's the kind of thing where maybe we could have a system for opting out, but we have to find an efficient solution for that system. So, there might be a system where rather than going back and checking that we have every individual person's consent, it could be more a system where people are informed that.

[00:33:49] Euzebiusz: This type of low risk research is taking place. And if you wish to opt out, then we have a mechanism to remove your data. Now that requires very slick data systems, which requires a lot of resources. But in many countries, like in Switzerland, for example, I'm sure a system like that could be created. and as you mentioned, provided.

The number of people opting out doesn't compromise research in general. We might be able to balance the individual versus the collective interest. if those things become unbalanced, I think that's a time for a conversation in society about, how we want research to be done.

[00:34:21] Angela: Thank you both so much for this. not always comfortable, but still very illuminating discussion. Do either of you have any last messages to give our listeners before we wrap up? Beenish?

For our part of the world, especially, ethics become, I would not say secondary, but we have to actually, Manage on the basis of what we have and what we have provided, We do think that ethics, play a big role in infectious diseases. And, there should, be adequate.

[00:34:49] Beenish: Resource allocation, adequate anti-microbials and vaccines for everyone. Ethics in,, Pakistan especially, it's a relatively new subject. introducing ethics into our, Framework that is also a big task for us. we can only implement these ethical, considerations once people are aware about them so the first thing we have to do is make people aware about ethical, uh, considerations or these ethical obligations or model.

[00:35:14] Beenish: as doctors especially. Those in the medicine or the ID field they need a lot of conversation and these ethics they need to be discussed.

Yeah. Thanks Beenish. Zeb, how about you?

[00:35:26] Euzebiusz: I would say, ID clinicians are running up against ethical issues all the time in their day-to-day practice.

we're moving from a model like we talked about, of blaming patients for not taking enough antibiotics to thinking about the minimum course that we need. And I think when clinicians run into ethical issues, , and they want to think about them more, they should find some people to talk about them with and collaborate.

thank you so much again to our guests. Zeb Jamrozik in Melbourne, Australia. And Beenish Sayed in Karachi, Pakistan. And thank you for listening to communicable the CMI Comms podcast. This episode was hosted by me, Angela Huttner in Geneva Switzerland, editor in chief at CMI Comms ESCMID's open Access Journal.

[00:36:05] Angela: It was edited and produced by Dr. Katie Hostettler-Oi and peer reviewed by Dr. Goulia Ohan of Yerevan State Medical University, Armenia. Theme music was composed and conducted by Joseph McDade. This episode will be citable with a written summary referenced by A DOI in the next eight weeks, and any literature we've discussed today can be found in the show notes.

You can subscribe to Communicable wherever you get your podcasts, or you can find it on ESCMID's website for the CMI Comms Journal. Thanks for listening and helping CMI, comms and ESCMID move the conversation in ID and clinical microbiology further along.