NIH All About Grants Podcast: ClinicalTrials.gov

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Dr. David Kosub: ClinicalTrials.gov, the world's largest database of publicly and privately funded clinical trials information. Millions of people visit the site every month to learn about what's going on in the world of clinical trials, but what do you, as a researcher, or as a NIH recipient organization, need to know about reporting your information, your trial results to ClinicalTrials.gov? My name is David Kosub, and this is NIH's "All About Grants."

>> From the National Institutes of Health in Bethesda, Maryland, this is "All About Grants."

Dr. David Kosub: I'm glad to say that we have with us Dr. Anna Fine. She is the acting director of ClinicalTrials.gov, which is housed within the National Library of Medicine, and I welcome you to the show, Anna.

Dr. Anna Fine: Thank you! Thanks for having me. Happy to be here.

Dr. David Kosub: Great, great. Well, let's just jump right in with an easy one: What is ClinicalTrials.gov, and what is someone going to find there?

Dr. Anna Fine: Oh, great question. Thanks for asking. So the ClinicalTrials.gov is a database and a website, and it contains research studies conducted around the world. We currently have over 460,000 studies listed with us, and you have easy access to search for the clinical trial information. As you mentioned, this is provided by the National Library of Medicine at the NIH. So, seeing that we are a library, we are a shelf where these studies can reside, free of charge. We're not the authors of the study, so having one listed on a government site does not actually mean that it's evaluated or endorsed by the federal government, but it is available for millions of users, including patients and advocates and researchers and health professionals, who search it daily.

Dr. David Kosub: And folks who are clinical trials aficionados are well-aware of the fact that NIH has a policy about reporting clinical trials information, but before we kind of jump in to some of that, it's important to explain why we like to ensure this information is reported to ClinicalTrials.gov. Can you kind of talk more about that?

Dr. Anna Fine: Yes. This is my favorite question, because we're passionate about transparency. Registering clinical trials when they begin, providing timely updates, submitting summary results and making the information publicly available fulfills a number of purposes, and it benefits a variety of people. For those who take part in the trials, they're making the information available that fulfills an ethical obligation, for those participants contributing to science and the body of information. Volunteers want their participation to help advanced medicine. And those who are seeking to conduct trials, it informs their research; what's been done? What other questions remain? How could I do a study better from what might have already been done? Subsequently informs decision where to invest, and assist with the good stewardship of limited research resources. Then not all studies and results information are published in literature, and literature can also have limitations. So a trial database provides the space, as well as a consistent structure. We've had studies that have been published, and they would be able to point right back to ClinicalTrials.gov from there, where you can find more information that didn't quite make it into the limited space of a journal article. Prospective registration also supports the ability to understand if the study fulfilled what you set out to do, so it really promotes research integrity. Having a reliable source for patients and organizations can seek trials, it supports enrollment. Registering with us can help these patients find the trials, and perhaps help your enrollment. So ClinicalTrials.gov makes the information about research available to the public in a very centralized place, that's free of charge, provided by our library.

Dr. David Kosub: So actually jumping off that, and making the information publicly available to anyone who's kind of looking at it, what kind of information is actually in there that's required as part of NIH-funded studies?

Dr. Anna Fine: Yes, absolutely. So I did say that you do need to register these studies when they first occur, because that's the whole prospective, making sure that fulfilled the question that you set out. You can't change your study along the way, as you're finding you're learning a better way that you could be responding to it. So sponsors, investigators need to provide a structured summary of the study protocol, why they're studying what they're studying, what are they studying? Who is conducting them, so people can find you if they have questions about your study, or patients might know who to reach out to. The status � who is eligible to participate, a little more about the demographics. Where is it taking place? Is it in multiple locations? Is it somewhere on the East Coast, the West Coast, overseas? Then of course, as I mentioned, the summaries are really important, because it helps people find and learn about what's ongoing and what might be completed. And then, of course, the information needs to be updated throughout the trial lifecycle. So if you're changing the recruitment -- you might have been recruiting a couple of months ago, but you're full -- it's really important, so patients know that. Maybe a new location became available, it became a really popular study, and you have the resources where you can maybe open another location -- that's an important update as well. And of course, if your research is complete, we're done, we're still kind of analyzing, you want to make sure you note that so patients do not get their hopes up if they see that something might be recruiting when it truly isn't. Finally, it's really important, your key research findings need to be submitted as well. The number of people who started -- are they the same amount of people that completed the study? What was the demographics? Are they people like me? Are they people like you? Can I identify with the people that participated in this? Do they have similar characteristics that I have? So that's part of their baseline measures. And then the outcomes -- we do collect statistical analysis, and of course if there's any serious or adverse events that occurred. That's important to include as well.

Dr. David Kosub: It definitely sounds like a lot of information out there that our researchers, our recipients are having to input in there. Can you talk more about what, exactly, the researchers must be doing, actually, as it relates to giving all of this information?

Dr. Anna Fine: Absolutely. Yes. If you are under the NIH policy, the dissemination policy for NIH-funded clinical trial information -- if you received any money from NIH, you are required to register, not just because it's such a great thing, as I discussed earlier, but because it's also a requirement as part of the condition of funding. And in doing that, if you started your study on or after 2017, the investigators are expected to register trials within 21 days after first enrolling your first participant. And you can't just register and forget it -- as I mentioned, the trial does need to be updated at least once per year, at minimum. And then there's requirements, as it does change there are some requirements. For example, if you change some of the contact information, or your recruitment status -- you have to actually update that record within 30 days of when that change has happened. You must also submit the results information, and it is one year after your final collection of data for your primary outcome, which is called your "primary completion date." So we call that your PCD plus one. And you can delay if there are, of course, challenges, or you have some additional times that's needed. There are ways you can actually delay on when you need to submit those results information. We have a process for that that we recently announced, called he NIH Good Cause Extension Request Process and Criteria Document. And of course, you do need to keep your contracts managers aware of all of this, and request a delay with them within NIH. So there's a lot of important milestones that you need to meet, and we do have a lot of information on our site, where you can learn a little bit about those, in making sure that you're keeping up to date with your requirements.

Dr. David Kosub: Right. I'll take a collective breath for all of the researchers out there and say, oh my gosh, that's a lot of things to keep in mind. But obviously, it's critically important as it relates to the NIH policy. Are there any other policies that researchers should be thinking about? I'll take the collective breath with them again.

Dr. Anna Fine: [LAUGHS] Absolutely. Yeah, there are many laws and policies around the world that are also supportive of transparency in trial reporting. The European Union has their own rules as well, and other regions and countries. The World Health Organization supports basic data elements that we also have for registration, and then within the U.S. there are other agencies, as conditions of funding, that also require you to register with ClinicalTrials.gov. As I summarize some of those basic requirements, they may do different details from country to country, or policy to policy. But the gist of it's the same. There is one key detail that I do want to actually point out. The International Committee of Medical Journal Editors -- if you'd like to publish, they do require registration of clinical trials before enrollment. There are slight differences that they require before the first participant is to be considered enrolled, whereas in the U.S. laws, it's within 21 days of first enrollment of a participant. I think that's really important if you want to publish, to just note that slight difference; that you want to register your trial just before you're conducting it. Don't wait, maybe, those 21 days, especially if publication's really important to you. Then of course, federal law beyond just NIH, there's dissemination policy -- it's implementing regulations, and so it's really important -- you need to submit results for certain clinical trials of FDA-regulated drugs, biologics and device products.

Dr. David Kosub: All right, well, we're breathing again. So we've gone through the information, we've talked a little bit about the policy, what people should be thinking about. A nuts and bolts type question -- what actually is the process of reporting into ClinicalTrials.gov?

Dr. Anna Fine: Yeah, we understand, investigators are really busy and don't have a lot of time. We try to make the process as easy as possible, but, you know, conducting a clinical trial is not that easy. It does take work, you know, preparing data tables, figures. It's similar to preparing for a journal article, where you need tables and you need certain sections, and you need to make sure you have the proper authorities, and people signing off on your literature that you'd like to publish. So first, investigators need to get access to the protocol registration result system, also known as the PRS. So the PRS is that web-based data entry submission portal that we have for ClinicalTrials.gov; it's just the ones where you, as the researcher or the investigator, that's how you're inputting your information that eventually shows up on our public website, which is called ClinicalTrials.gov. Organizations that conduct clinical trials, such as academic medical centers, they generally administer and provide their investigators with access to a PRS account, so you might have one administrator at your university academic center that has the ability to provide accounts for each of the investigators there, and helps manage those. Next, we have the investigators, or the staff, need to enter the information about their clinical trial, or the results. And they go through a bunch of data elements on the form that are required, and there's very few that are volunteer. We ask you all the things that are absolutely necessary; we don't want to ask for too much, because we know you're so busy. The PRS does provide extensive online and Just In Time Health, that's some of the improvements that we've also been looking to make as we're modernizing the system. So as you're entering it, and you're wondering, well, what do I put here? What are you asking for? What kind of date am I putting in here? There's definitions right off to the side that you can click on as you're going through, that helps to explain a little more of what those data elements are. Then, of course, we do have staff that can assist with any submission questions you have, by email, phone. We've done video conferences. We do want to support you in having to do this. Once you enter the information, in some organizations, you know, if there are administrators, or you might have another individual within the study, they might review and help approve, making sure that you are, just before you're hitting submission, making sure that everything's there that needs to be there, and able to release the record to us. Records do come to us. As I said, they're not endorsed or really reviewed by government. It's more of a quality control review, like a library. Is the title there? Is there an author? Does it actually have pages? Does it have a title page? Does it have sort of a prologue -- those are some of the basic things that we're looking for. You know, is it in English? We're just looking for apparent errors or deficiencies or inconsistencies, just to make sure that you're putting the right information in the right sections, and that it's being consistent. You know, if you said you're studying 100 patients, did you only account for maybe 40 in your adverse events, or whatever section that it might be relevant -- we just review consistency. So then that information, for the registration, takes a few days before it becomes on our site. For the results information, as you know, it's a little more complicated as you're pulling together and summarizing all your data. So that takes generally up to about a month before it would be available on our site.

Dr. David Kosub: It reminds me that I need to get my library books checked back in now, all those titles checked out. Well, thank you very much, Anna. This has been great. Before we leave, are there any other final thoughts you might want to leave with our audience, about ClinicalTrials.gov reporting, and all that?

Dr. Anna Fine: Oh. I think I just want to remind listeners that we're here to support you. We're here, we know it's not easy. We know the work you do, the good work that you're doing, we want to support you the best that we can, so if you have questions or problems, you can reach us, email us at Register@clinicaltrials.gov. Also, just keep in mind that ensuring transparency and accountability is really good stewardship of NIH funds, and it's a shared commitment between NIH and investigators. We are your partner in achieving these important goals, that you can learn more about any updates that we have. We have a Hot Off the PRS e-newsletter, and there's a wealth of information on our site to help you with learning a little more about what your commitments are. So thank you for letting me share that information.

Dr. David Kosub: Absolutely. Thank you very much, Anna. This has been a great opportunity to learn more about the reporting requirements for ClinicalTrials.gov, and what our researchers should be thinking about. I encourage everyone to go check out the resources that she mentioned; the Hot Off the PRS, Hot Off The Press Newsletter, I love that title. And ask them questions, if you experience any issues, or have any comments or questions. They want to hear from you. This has been David Kosub with NIH's All About Grants. Thank you.