 Menecoff is the Director of the Office of Human Subjects Protections in the US Department of Health and Human Services. There he works to protect the rights, welfare, and well-being of HHS research subjects. Dr. Menecoff previously served as the Director of the NIH Office of Human Subjects Research. Additionally, he served on the Human Subjects Committee and the Hospital Ethics Committee at the University of Kansas Medical Center and was an Associate Professor of Law Ethics and Medicine at the University of Kansas. Dr. Menecoff has authored two books and numerous academic works, which concentrate on bioethics and the use of human subjects in medical research. I'll just go off script here and add that he's from the best fellowship class, which was the one that I was in also. Dr. Uble, Dr. Angelos, it was a great class. And so today, Dr. Menecoff will be giving a talk titled Viewing Research Consent as Similar to Clinical Consent. Please join me in welcoming Dr. Menecoff. I particularly want to thank Mark for the invitation to be here. It's a great privilege on a number of grounds, particularly after those moving tributes to Bill Meadow. I didn't know him as well as I would have liked, but there were various interactions we had. And my recollection is we actually disagreed quite frequently, but he thought what I was saying was important enough to vocally disagree with. And I view that as a great privilege, so. And particularly with regard to John's point about his no bullshit principle, I think that's the core of what I'm going to talk about here. Can we improve research consent and basically get rid of the BS in terms of doing that? No conflicts. I do want to note, I work for the federal government. Virtually everything I'm going to tell you is going to be my opinions. Don't view any of this as being the official opinion of any part of the federal government. What I am going to talk about is the relationship between research consent and clinical consent. I'm going to make an argument that actually we should view research. Often we view research as a whole different animal, that it has all these arcane rules. And for a type of research study where we really are dealing with somebody with a medical problem, particularly a difficult medical problem, and perhaps current care is not particularly good, the decision about being in the research study should be viewed more like a decision that we make in the clinical context. And it's interesting the wake of all these superb talks earlier today about the difficulties in the clinical context, particularly in terms of surgery, that we don't do that great a job. Well, hopefully we still do a pretty good job, and maybe we could do a better job in the research context. Again, by viewing a lot of these research studies is more akin to clinical care decisions. So that's where I'm going to try to go. And this is going to be in the context of, I am part of a federal agency, we did actually change the rules relating to enrolling people in certain types of research studies. And I would like to argue that sometimes the rationale for changing rules is to further advance the underlying ethical thinking. And hopefully some of these changes actually are really, really good changes. But we'll see. OK, so what I'm talking about are what I would call treatment clinical trials. Again, somebody who has a medical problem and they have to make a decision about being in this trial. And some points about this sort of decision, clinical decision making is often complicated. And we know, we've heard about how hard it is to get good consent. Some clinical trials involve basically asking somebody who has a medical problem to enroll in the trial and perhaps have something happen to them that, from my viewpoint, in the past you'd often have people who would say, you can never even use the word treatment in a clinical trial because it's not treatment. You're getting some sort of research done to you as if that cannot be treatment. And that's, again, used a BS test here. That is BS, from the viewpoint of somebody who has a medical problem and is a sort of narrow window in which they could get a treatment for that. If they're enrolling in a clinical trial, they are making a clinical treatment decision. Let's treat it as that. Let's be very upfront with them, do better consent. And note, these sorts of decisions are actually even more complicated than a lot of other clinical decisions because one of the things that often shows up in a lot of trials is we're doing randomization. And that's extraordinarily difficult to wrap your mind around. How many times do we do anything in normal life in which we'll say, well, instead of deciding to do A or deciding to do B, we're gonna be randomized, which means, well, either of those things can happen to you. And how do you, again, wrap your mind around that? That is just a really, really hard thing to do. So anyhow, I noted, here's a link to the changes in the federal regulations, which I will give you a bit of a sense of, again, just my personal take on what I think the changes are trying to do and is my personal take that you could read a lot of these revisions, the general revisions relating to improving informed consent, which I think by a far margin, by a wide margin, are the most important element of the recent changes to the regulations, that these changes, in fact, do fit with thinking about research consent as more akin to clinical consent in certain types of trials. And so one of the things that you benefit from here are that we already have a lot of learning about how to do clinical consent. Let's use the learning to the extent we actually are doing a good job in terms of clinical consent to do a better job in terms of research consent. And this is just noting some of the practices that are common in making clinical decisions. So the theme here is that it's not so much kind of giving people pieces of information, risks, benefits, alternatives, but you have to put it all together. Again, get rid of the BS and explain to somebody what is a complicated decision and how to think their way through it. And common scenario that we're all aware of, yet we don't do anything about it in terms of research consent forms. Every research consent form, almost like cookie cutters, every side effect at a drug you might get in the research trial has listed in, you know, PDR, whatever. In clinical consent, do we do that? No, we never do that. That's absurd. I mean, we know from Komin and Swarovski, if you go past three pieces of information, the person's mind blurs over and they can no longer make a decision. So instead, we give them 10 pages of grids on, well, here are 80 risks that this drug will give you and here's the second drug you're gonna get and here are 60 risks and here's the likelihood of each of them and here's how serious they are and like, right, you're gonna be able to make a decision about that. Okay, so now let's get to revised common rule. It highlights, and this may sound incredibly obvious, but often it really is important to, again, get rid of the BS and point out. There is a choice being made. If you could take your own take about what current consent forms in the research setting do, but many of them do sound like they're, and this echoes some themes we heard earlier today about the clinical world too, they almost sound like legalistic things that we're gonna disclose every risk possible so that you cannot sue us down the road when one of these risks takes place and et cetera, et cetera. And that's actually, you know, implying that we're, again, we're trying to get you into the research study. Instead, it should be about there really is a decision to be made, let's help the person make the decision. And one thing to think about the last point here, ask yourself in terms of research consent forms because this is something you could really check. Find how many times in research consent forms they actually spell out, here are legitimate reasons why you may not want to enroll in this research study. And I've looked at lots and lots of consent forms over many years and not exactly a lot of verbiage spent on that point. And there's a reason because, again, these forms are typically written in a way that of course you're trying to kinda get the person to say yes, and the moment you give them a reason that's spelled out, why you might wanna say no, they might actually think about that and say no, and that's not what you want them to do. So you're doing what you have to do, yes, I have to tell you the risks, but who cares? Yeah, okay, so compare it to, for example, the drug ads on TV, which will go on and on about all these horrible risks, and they are horrible risks, right? And they're almost like dancing in front of you, telling you, well, there's a 10% risk you're gonna die from this drug or whatever it is, but the people in the video behind them are like having a great time and smiling and laughing and all that sort of stuff, and these ads work, okay? But of course the one thing they won't tell you about is the alternatives, like are there other things you might wanna consider instead of these drugs, that sort of stuff. So bottom line, let's think about how, what do we already know about how you give people information to actually genuinely tell them there is a decision to be made, how could we make a better decision? See, here's some of the actual changes in the regulations, and again, a lot of this may seem like it's incredibly obvious, but all the stuff I've highlighted and read, they are words that are not currently in the federal regulations, and it seemed worth putting it in there so that researchers could be told. Yes, it's about letting the person make an informed decision about whether to participate. It uses the reasonable person standard, it's a standard that's been used in the legal context, we can have an extensive debate about whether it's good or bad, but note the important thing is this is an alternative to another standard that is still used in many states, which is basically the professional standard, that how do you figure out the information you give to somebody when you're asking to make a clinical decision, the doctors decide that. And over time it was determined by smart judges that the ethically more appropriate standard is what's called the reasonable person standard. Once we know the side effects of particular treatment, ordinary people could then figure out, would I wanna know about the 10% chance that I'm gonna be paralyzed after this surgery? The fact that a whole bunch of doctors said, nah, because this is true, in this scenario that led to this particular legal decision, they wouldn't tell you that, and that was the end of the debate, it was the end of the lawsuit. So it now has this as part of the standard under the rules. The information has to be in sufficient detail, organized and presented in a way that facilitates the subject understanding of the reasons why you might or might not wanna participate, not merely a list of isolated facts. So again, and in terms of isolated facts, here's your little block about risks, here's your little block about benefits, here's your little block about alternatives. Again, think back about some of the, was it Dr. Schwartz's talk earlier today, there are ways of actually having a good conversation with a patient and explaining the relationship of those things that the person could get a better sense of, well, would I or would I not really wanna be in this trial? But you're not making it easy for them by saying, here are the risks, here are the benefits, here are the alternatives, you figure it out, even though it's like really complicated due to the fact that a lot of medical care is complicated, plus you've now thrown in often a randomized decision. What does that mean? So that's what it's getting at, not just a list of isolated facts, spell it out, explain to the person, and these again are now rules that people are bound by, and this is just sufficient detail. So common thing, I'm sure a lot of you have seen this in benefits discussions, for example, because some people will say, well, our consent forms are already overwhelmed with detail. Actually, it could be there's not enough detail on the few little pieces that actually matter. So for example, benefits, you may or may not benefit. What in God's name does that mean? I actually did a little study when I was NIH just asking people in waiting rooms or something, what's your likelihood, we gave them part of a sample consent form, what's your percentage likelihood of benefiting from being this trial? And we randomized them to different pieces of language, and several language words you may or may not benefit. And a lot of them said 50%. It's an important trial, tens of millions of dollars are being spent on it by NIH or something, you didn't give me a percentage. There must be a substantial chance I'm gonna benefit, which of course is, and this is in context of phase one trials. So not merely list, I kind of told you about that. There's a new requirement that key information should be provided first, and the notion again, consent forms are long, keep getting longer. The key stuff, the stuff that really matters to most people, you can probably lay out in a few pages. So if you have a 20, 30 page form, figure out what matters, explain that to the person in the first two or three pages, and hopefully they'll actually better understand than they do with the current consent forms. Again, we talked about why you might and might not wanna participate, concise and focused. And so let me just close with an example. This was from 10, 15 years ago, but this is a real study. So a woman who has breast cancer, and she's gotten the initial treatment, which was chemotherapy and surgery. And at the time, there was a lack of understanding about the best way to treat a woman who after they'd done the surgery, they found one to three positive nodes. And the question was, should you add radiation or not add radiation? And there was a randomized study to randomize the women to either getting radiation or not getting radiation. And the consent form basically had part of a sentence discussing the rationale for why this study was being conducted to find out whether adding the radiation treatment will reduce the risk of breast cancer reoccurrence and help the patients to live longer. And the interesting thing, because I think this makes it a great example, is that at the time this study was happening, there was actually a newspaper article in the New York Times about this. And it's very well written. I mean, New York Times had some wonderful science writers. Oh, Lori Tarkin wrote this piece. And what it interestingly discussed was decision making in the clinical context. Now this is fascinating because if you read the article, which wasn't mind boggling long, it would take you five minutes to read it or something, a huge amount of information you did not get from the research consent form, which is fascinating because allegedly on the research side we are far more articulate about spelling out things because it's research. And we're not necessarily recommending something that we pretty much agree is sort of standard therapy or whatever else. And what was laid out in that article was, for example, that we knew that women with four or more positive nodes, for them adding radiation increased survival. And that the benefits gradually seemed to go down sort of linearly as you had fewer and fewer positive nodes. But here's a quote from the article. There is no question that if given radiation, these women would further reduce the risk of recurrence by two thirds, bringing it down to three to five percent. Now wrap your mind about that around that, okay? We knew that you would dramatically reduce the likelihood of the cancer coming back if you gave the woman the radiation. What we didn't know is if she would live longer as a result of that. But you might ask yourself, well wouldn't a lot of women actually care about that middle bullet there? Regardless of whether we know it's gonna extend the woman's life, maybe she doesn't wanna wake up three or four or five years from now, confronting with an issue of what do I do now? They just told me that the cancer recurred. Not in the consent form. There was a half a sentence about the rationale for all this. So let's kind of play out the no BS version of this consent form. Include more specific information to the information that was in the New York Times article here. Would a reasonable woman wanna know this point about adding the radiation and reducing the likelihood of recurrence? Duh, I think so. So should the consent form perhaps explain how the woman, based on her values, might wanna use this information in reaching a decision? Could point out that a woman who wanted to minimize the chance of the cancer coming back, even at the risk of getting radiation which may cause side effects, et cetera, et cetera. And even if it's not clear that it extends her life, some women would say, of course I want the radiation. And they shouldn't be in the trial. And the consent form should spell that out. It shouldn't be for her to kind of puzzle all this out or not give her the information that she needs to make that decision. And there may be a very different woman, okay, based on her life, maybe she doesn't have children, whatever else or something, that she's very concerned about the side effects of radiation if it isn't clear that the radiation is actually gonna do anything in terms of her extending her life. And maybe she's concerned about, again, those side lymphedema, whatever else. So she very much might want to, again, just not get the radiation and therefore not be randomized. So, again, depends on your values, but you could spell all this out. So that's the end of it and I guess we have time for questions. Thank you for staying on time. We'll take a couple of short questions because we're running behind, thanks. Hi, thank you so much. What I'm interested in is the approach to how you figure out the disclosure is very clear how you will go about figuring out things in disclosure, but when you're crossing race, class, and culture, the question is what barriers are there to doing that because nobody really deals with that. Some years ago, I shot about 200 hours of footage about doing disclosure for palliative care. And one of the things that we found out from analyzing that footage is that barriers included issues around family, issues around struggles in the past, issues around whether or not how people presented with the icons of their culture, so how embedded they were in the cultures that they came from, and spirituality. But there has to be some format for you to go through because the reason people don't go into that is because they're like, oh, healthcare literacy is just so complicated. We can't do that in this process. So different paradigms have to be set up to deal with the race, class, and culture, and I'm wondering if you have looked at that as it's not just the disclosure, right, but it is the other part of the disclosure, the barriers to disclosure. Yeah, now you certainly raise wonderful issues. This is all complicated, and it'll probably, again, depend on the type of study, and particularly what groups you're likely to encounter in terms of prospective subjects. To the extent you could delve into further aspects of fine-tuning the information relating to these various cultural and specific population group concerns. They are great issues. It gets back to these trade-offs about trying to minimally do enough in terms of your generic person, and then dealing with the further layers and complications from, as you say, values, cultural backgrounds, et cetera, et cetera. I might say that I also had the responsibility as a bioethicist to actually deal with the AZT oral trials in Cote d'Ivoire that happened about 10 years ago, and this is what we unburied, is that you almost have to start backwards and then go forwards because the exercise of starting with that component actually allows you to have a better chance of getting more information through in the disclosure. Thank you, September. One more question? Hi, thank you for this. So you mentioned the reasonable person standard and the inclusion of this new standard within the revised common rule, but that really pertains to liability, and so I wonder if you could speak a little bit to the fact that the revised common rule still doesn't allow generally for a private right of action for informed consent and research, as it does in the treatment context. So while we're talking about bringing research informed consent closer to clinical informed consent, we still don't really have a right to sue, a participant doesn't usually have a right to sue the researcher for failure of informed consent if something goes wrong. I guess from my view point, I wouldn't have viewed the reasonable person standard as at least in this context, a liability standard. It's about giving the person information that really matters to them, and I think that standard will help make sure that consent forms, you know, zoom in on the first one, two, three pages on the most important information and just don't leave out additional information. In terms of being able to sue, the federal rules, and those are the ones I generally deal with more, don't create a right of action, but you do have a, I mean, this is all state law. I mean, I don't want to get into weeds in terms of the lawyerly stuff. Obviously there are toward actions that could be brought by and large, and it's an interesting question. Either people don't bring a lot of those actions or they're not successfully winning them or some of them are being settled, whatever it is. That is an interesting fact that bears further analysis given how litigious this society in general is, but the right is there. I mean, you certainly can sue and you certainly can win for research malpractice, but it's a state cause of action. How it will tie into if the standards for writing a good consent form are improved, I suspect it will make it easier to bring a lawsuit when somebody deviates from those standards. And one thing I didn't note is, and I think this is a big deal, we are now making most consent forms out there that come under these rules public. So you could go on a website and find out many, many consent forms, which I suspect a lot of lawyers are very happy to know that, and a lot of bioethics scholars, because they could now look at all of this and we could learn from those consent forms, figure out which are better, which are worse, test them, and then improve them. So, yeah, thanks.