Major: Hey guys, welcome to the DarshanTalks Podcast. Today, we're going to be talking about the six components of a clinical trial transparency program. My name is Major Hoffman and I'm here with Darshan Kulkarni.
Darshan: Yep. That's still my name.
Narrator: Good. Just double checking. This is the Darshan Talks Podcast, regulatory guy, irregular podcast with host Darshan Kulkarni. You can find the show on Twitter @darshantalks, or the show's website at darshantalks.com.
Major: Darshan, can you briefly go over why you would need a clinical trial transparency program?
Darshan: So, one of the big reasons you want a clinical trial transparency program is because you're legally required to actually disclose... Components of having a clinical trial transparency program are legally required. So, if that's part of it, you might as well have a system around it, so that it's comprehensive, and you aren't trying to reinvent the wheel every single time. So, that's one big reason.
Another reason to do it is because it's the right thing to do. And you might want to do this because you're being a patient centric organization, and that's often the core values of a lot of different companies. And you might also be looking at having a clinical trial transparency program because it's trying to figure out how this fits into some of the other components that you're already managing. So, we can have a whole discussion about this, but those are some initial jump off considerations as to why [crosstalk 00:01:23].
Major: Right, I'm sure someone's like, we need to have a clinical trial transparency program, and I think in a previous discussion, you and I said or you mentioned this, this can be considered to be monolithic, and it doesn't have to be like that. And that's what we're trying to get into. Is theirs, out of all the different components or you've summarized those, or you've collectively put them in a list of six components of a clinical trial transparency program. So, without further ado, what is number one?
Darshan: So, the reason I mentioned a model, is most people think I want to have a clinical trial transparency program, and I have an answer to it. They think it's a question with a direct answer. Unfortunately, like we mentioned, there are at least six different components, and these six different components may have different answers. Each component may have a different answer than when compared to someone else. So, don't think of it as a monolith. Think of it as a jigsaw puzzle, and only you know what that final picture needs to look like.
So, the first component to that is a requirement if you are conducting studies, for example, in the U.S. or have U.S. implications, or using U.S. patients. You need to actually register your study depending on which type of study it is, under clinicaltrials.gov, which is the main website most companies use. So, it's clinicaltrials.gov. You also have the European version, which is EUDRACT, and that's E-U-D-R-A-CT. The EUDRACT website is not as active as the clinicaltrials.gov website. I think the last time I looked at it in one year, EUDRACT had something like 1500 studies and that same year clinicaltrials.gov had something like 19,000 studies.
Major: When you say clinical trial registration, do you mean registration of the clinical trial or clinical trial of participants in that clinical trial?
Darshan: So, what I'm talking about is the registration of the study that the study exists. So, this might actually be a tool for patients to register and say that I want to be part of the clinical trial, but this is not the place you'd go to, to register as a patient. It simply is where you go to, to say, I have a study. The second one is actually having a result. The results of those studies need to be disclosed. So, you EUDRACT or clinicaltrials.gov may require for certain types of studies that you disclose the results of those studies. This way patients who participate in this study can understand that... How should I put this? Patients who participate in this study can understand the results of the studies that they participated in. One of the big problems you have in the pharma industry is that we get the help of patients, get the help of subjects, and then at the end of it, we forget that we need to close that loop. And they're left in the dark, and this reporting requirement, the results reporting requirement was a way to fix that.
Luckily, there's also a... And that's pharma companies. We should also make it clear that if you are a physician, there's actually a requirement in the declaration of Helsinki, and this hearkens back to anyone who's done any kind of bioethics course, but declaration of Helsinki, specifically states that researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of the reports. So, it's important that if you are a university doing studies, if you are a physician working for a university doing studies, those results must be reported appropriately. So, that's two so far, right, major?
Major: All right. So, yeah, number one, clinical trial registration. Registering that specific clinical trial to say the study exists. And then number two, clinical trial results reporting. Making sure that you report the results, close loops, so to speak.
Darshan: Exactly right. The third one is the clinical study report redaction. So, when you're talking about Health Canada, which is the Canadian version of the FDA, or you're talking about the EMA, which is the European version of the FDA, they actually require that you disclose the actual clinical study report and make it public. And essentially what that comes down to is each of them has requirements where you will essentially make that entire application, well, the CSR components of it, available for the public to read. And the only things you can redact on there primarily relate to confidential business information. And there are requirements and rules around what that means, so it's not a willy-nilly, I think this is confidential. It's have you ever disclosed it before? Is this unique to you, types of questions that need to be asked.
And then there's the actual patient private information. So, there's a whole question around are you appropriately redacting private information belonging to patients? So, that would be also part of the clinical study report redaction. And that's another component of transparency. How are you as an organization going to have systems in place to ensure that while you're disclosing your clinical study report, you don't disclose your crown jewels and you don't disclose patient private information. So, that's your number three. Should we keep going, Major?
Major: I mean, we're only halfway through, right?
Darshan: Only halfway through.
Major: I feel like the rest... I'll talk about that after we go through it but go ahead and continue with number four.
Darshan: So, so far what we've talked about is really existence of a study, or we were talking of the results from that study, or we've talked about the redaction of the actual report. However, the EMA has taken it one step further and basically said, we want you to disclose the actual raw data. So, if you participated in a clinical trial, we want you to... Sorry, if you ran a clinical study, we want you to disclose the raw data in an anonymized form, and it must be disclosed appropriately. Several companies in the U.S. are already doing that, and they had had their own systems in place. However, there's a need to go further. This obviously has major privacy implications, but also has major implications on your publication's strategy. And what I mean by that is that ICMJ basically, which is the International Medical Journals Editor Group, basically they came out and they said that we will not publish your clinical trial reports and your study results, unless we can actually look at the raw data. How do we know that you aren't lying to us? So, that's where that came from.
And then you also have to remember that clinical trial disclosure is often a requirement, part of a Bio and AdvaMed and Pharma requirements. So, keep track of not just what's required legally, but are you following what these other organizations are requiring? Whether it's ICMJ or Bio, AdvaMed, Pharma, et cetera. That's number four.
Major: So, clinical trial registration, number one. Number two, clinical trial results reporting.
Darshan: Correct.
Major: Close the loop, report the results for participants. Number three, clinical trial report redaction. Identify what you can redact. Don't disclose a family jewels of the clinical trial or the patient data.
Darshan: Correct.
Major: Number four, clinical trial data disclosure. This goes into the ICMJE.
Darshan: Correct, ICMJ.
Major: How would you summarize number four though? The clinical trial data disclosure. Because wouldn't that be similar, sort of like...
Darshan: To number three?
Major: Yeah.
Darshan: So, number three is really your actual application to the FDA. So, it's the actual written form where you're saying, this is what my study is. This is what we disclose. This is why it matters. On the other hand, number four, which is your data disclosure is the basis of that report disclosure.
Major: So, you're actually disclosing the data.
Darshan: Correct.
Major: What the report was written from.
Darshan: Correct.
Major: Okay.
Darshan: So, when people say that pharma companies are opaque and you can't look at, you have no idea what they're doing, I don't know how much more transparent you can get then, here's the actual raw data we used.
Major: And in that raw data, I'm sure you would have some redactions as well, right? In terms of the patient data.
Darshan: So, you would redact not the data itself, but you'll probably land up redacting patient names and you'd de-identify the data basically.
Major: So, you'd scrub it for identifying info.
Darshan: Correct. Now, you've still got to be careful about how you do it, because if you do it wrong, patients can be re-identified using other data sources.
Major: Right. Right.
Darshan: So, it's complicated about how you set that up.
Major: Who would approve that? When you do scrub identifying information, is there some sort of...
Darshan: Well, there's a statistical standard you use to make sure that that's statistical standard. And again, you've got fines and penalties if you don't redact appropriately. So, that's really... And redaction's just one way. There are other ways to also de-identify patients. So, for example, if you're dealing with... One of the methods of de-identification is generalization. And what I mean by that is instead of saying 70-year-old, white male in Pennsylvania, you might say, someone between the ages of 63 to 74, living on the east coast and is a Caucasian male. And that makes...
Major: Further abstracted.
Darshan: Exactly. Exactly. That's one way to do it. There are other ways, including number shifting strategies, et cetera, which keeps confidential information confidential, but nevertheless allows for the data disclosure to happen. So, it has no impact on your statistical analysis, but it should still allow you to redact appropriately. So, that is another strategy that gets considered. And again, we can do [inaudible 00:12:21].
Major: Right, so that was number four. We've got two more to go. What's number five?
Darshan: Number five is, we talked about ICMJ earlier, where we talked about these publication requirements. And what that is, is essentially these journal editors basically came out and said, we don't know whether to trust you guys. We don't know whether we believe that your data's accurate. So, you need to have a clear organization off your system that allows you to be clear about number one, which study are you going to first try to publish? Is it going to be all of them? Is it going to be only phase two studies and above? Is it going to be only interventional studies, et cetera, et cetera, et cetera? You're going to get that information together. You may also need to consider, how are you going to connect that to your data packet? Which was in the clinical data disclosure discussion we just had. So, you need to have a overall publication strategy and publications program. So, that's number five.
Major: Okay.
Darshan: And the last one is what we hinted at when we started, which was lay summaries. So, you've got all this data that's really geared more towards whether it's researchers or data scientists, or just other researchers who are doing clinical trials. This was an attempt by the EMA to basically go, it's great that you're saying that we're going to put out information. We need you to make it understandable to patients, to subject.
So, lay summaries came out of that. So, if you're publishing an article in the New [Inaudible 00:14:02] Journal of Medicine, we expect you to put out a simplified version, and it's not necessarily a either, or situation. EMA basically says, we need you to put out lay summaries around your studies themselves. Some medical journals have gone so far as to require the same thing as well. So, it's another component of transparency. Now you might say, is it just a requirement from a regulatory perspective, and is there clarity on how that happens? There are a lot of blank spots on how to do that appropriately. And there's a lot of research on that as well.
Major: How does this tie into number two? Number two, being the clinical trial results reporting. I mean, specifically, this is lay summaries, right? Number two is just straight up reporting. You have to report.
Darshan: Great point. So, clinical trial results reporting is really geared towards the researchers. So, the data is put out in a short version in chunks of information that are understandable to researchers, but they're using big words and they're using it in a way that researchers will understand. It's not geared towards patients. On the other hand, lay summaries is geared towards patients. Does that make sense?
Major: Okay. Absolutely.
Darshan: Awesome. So, Major, do you want to summarize the six components?
Major: Sure. Six components being, number one, the clinical trial registration. You need to register the specific clinical trial to say the study exists. Number two, the clinical trial results reporting. It's where you close the loop when you report the results for participants. I mean, because we just said lay summaries was really, well, for everyone.
Darshan: It's really for everyone.
Major: Okay. Number three...
Darshan: The big thing as you pointed out, is it's really intended to be for researchers because the way it's phrased is not patient friendly. However, you see patients use it all the time.
Major: Right. Well, with a focus on researchers, of course, participants will have access as well. Number three, clinical study report redaction. Is this where you identify what you don't disclose? Like you don't disclose the family jewels of the clinical trials you've said, or the patient data. And this is the actual written form to the FDA.
Number four, clinical data disclosure. This is where the actual data of the clinical trial results are released and it's important here to use recognized methods to scrub patient info, for example, with identifying information. That was discussed. Number five, publications program. Have a program publication strategy. That was the big takeaway for that. Number six, lay summaries of that report. Publish a lay summary version or a simplified version of that report.
Darshan: Exactly, right.
Major: That was it.
Darshan: Yep. Awesome. If you have any questions, feel free to reach out to us. You can find us on Twitter @darshantalks, or you can find us via the internet and [crosstalk 00:17:03].
Major: Good old internet. So, go to the post for this episode on the website at darshantalks.com and join our newsletter to obtain an infographic of this topic of what we just discussed. And we'll see you guys next time.
Darshan: Awesome. Thank you.
Narrator: This is the DarshanTalks Podcast. Regulatory guy, irregular podcast with host Darshan Kulkarni. You can find the show on Twitter @darshantalks or the show's website at darshantalks.com.