Within most clinical trials, sponsors commonly wait for a patient's site visit to enter concomitant medication data. Unfortunately, relying on the patient's ability to recall all the different medications and doses they have taken between site visits can lead to inaccuracies in the data and increase potential for human error.
How then can those involved in clinical trials gather real-time medication information in a way that both ensures accuracy and eases the burden for the patients involved?
Watch this webinar recording to learn:
- How to collect concomitant medication data with eDiaries.
- Recommendations from leading regulatory agencies for collecting concomitant medication data in clinical trials.
- Preferred methods of data entry across elderly patient populations.
Good morning and good afternoon, everybody, and welcome to the CRF Health webinar entitled Revolutionizing Concomitant Medication Capture in Clinical Trials.
So the webinar today will be presented by myself, Karl McEvoy. I’m the Manager of the Health Outcomes Team here at CRF Health and I’m based in our London office. And I’m joined by my colleague, Nora Ibrahimova, who is one of our Product Managers here at CRF Health. And we both make up part of the product and service management team.
The agenda for today is quite short. We will go through it. I’ll start, I’ll lead in, give the background on the topic. Some of the benefits and current challenges. And I’ll switch over to Nora, who’ll give you a bit of a background on how and why we developed this TrialMax ConMed solution, as well as some of the usability testing and work we did to get something that was a really well-rounded and beneficial solution. We’ll then go on to talk about considerations for use, and some of the things you can think about moving forward for the future use of a ConMed solution when done electronically and how that can tie in with some of the technologies that we’re seeing emerge within the clinical trial space.
So before we start, it would be very nice to get a kind of temperature gauge within the room and see, of those of you who joined, who actually does use concomitant medication collection within your studies. So you’ll see on the middle of your screen you’re given the option to vote. It would be great if you could select one of the answers, based on your experience with concomitant medication information collection over the last year. I’ll leave that open for a moment and we’ll see how the results come in. And we’ll have a look at the results in about a moment or so.
Great. Thank you very much for your responses. A greatly resounding result there, that yes, you do collect concomitant medication in your studies. I guess we didn’t really expect to see an answer other than that, given the topic of the webinar, but it doesn’t really hammer home the importance of concomitant medication collection within clinical trials and how it really is something that although we might not talk about day to day in normal studies, that it’s something that is at the forefront of our minds when we’re setting up and designing a protocol, particularly when we’re heading forward to daily diaries and site use.
So for me, whenever I think about concomitant medication use, this quotation from the FDA Guidance for Industry on Drug Interaction Studies is what springs to mind. I’ll leave it up on display there for everybody to read. It’s quite long to read out over the line. But in a nutshell, it basically mentions that concomitant medications can change, so the metabolism or drug transport system can be changed by the use of concomitant medication. And these changes can affect the known safety and efficacy of a drug. Some really common examples and well-known examples within the media for example.
would be warfarin and aspirin, so two drugs essentially thinning the blood, or over-thinning. Statins are so widely used these days, and for a very long time people didn’t realize that there were additional drug interactions, and even food supplement interactions happening. For example, with vitamin B12, niacin, or even grapefruit juice, having an effect on statins within the body. Other common examples would be blood pressure medications and use of decongestants, where they can introduce adverse events or symptoms that we don’t necessarily factor in when we’re looking at the main drug. Or the fact that in a pain study, where you’re testing a new pain product, the patient might actually be taking a whole range of other products, from topical ointments to over-the-counter medications, and we might see that as having an effect, but in actual fact it’s not a drug we’re testing, it’s the other medication in combination.
So guidance for concomitant medication capture electronically is pretty scarce, we don’t see too many references to ConMed
collection, specifically electronically. But anecdotally we’ve had a lot of evidence from our clients, and we’ve seen more and more a push towards having concomitant medication done electronically.
So more of the quotes that we see—I’ll just take some examples here as common results. So the FDA Guidance for Industry on the Structure and Content of Clinical Trial Reports, in Section 9.4.7, it mentions that “permitted or prohibited concomitant medications should be described.” The EMA says something very similar in their Guideline on the investigation of drug interactions, and so in Section 5.4.7, “documentation about doses of concomitant drugs need to be properly recorded, including the dose and timing of these doses.” And then, quite oddly, while we don’t see a lot of specific quotations related to concomitant medication, the FDA Guidance on Rifaximin, or in the use of traveller’s diarrhea, in Section 13, says that “the start and stop date of concomitant medication use during the study should be provided in the data set, in addition to the reason for that medication use.” So though we’re not specifically seeing mention of electronic use here, here at CRF Health and talking to some of our sponsors and some of our clients, we’ve had anecdotal evidence that the regulators are starting to ask specifically for electronic use, when we’re talking about the capture of concomitant medication. We had one example recently where acupuncture was listed as something that the sponsor needed to collect, and they said specifically that that data needed to be collected via an electronic system in the concomitant medication capture.
So again, it is an important system, but we don’t—at least on paper—see examples of it being done electronically.
And that brings us to our next polling question. So again, just to get a feel for the room and see how many of you have discussed collecting concomitant medication with regulators in the past year. And we’ll leave that poll open for about a minute.
Great. So that’s actually quite an unusual response, and it’s not something that we thought we were going to see, given the audience in the room today. Something that we found quite strange when talking to some of our sponsors and some of the clients, is that although there’s not necessarily written recommendations for electronic ConMeds, people do collect it but don’t necessarily go to the regulators to ask for more specific information about it. Again, this can depend on therapeutic areas, so you might not see it as being so important in your study, but it is something that we’ve seen becoming more and more common.
So we appreciate that ConMed collection is pretty important, we see that the effect of other drugs on the study drug in question can be highly relevant to the outcome of the clinical trial and indeed the safety profile of that drug. But you know, obviously there are challenges with the methods that we see for the collection of it on paper. And these tie in with some of the challenges we see in the traditional collecting of data in a clinical trial in paper mode. But as we’ve moved as an industry from going more towards paper-recorded patient-reported outcomes and clinical outcome assessments towards eCOA, things like ConMed collection haven’t really moved as quickly as the rest of the industry, so where EDC has changed about 10-15 years ago, and the electronic use of PROs and ClinROs has moved, we haven’t really seen that need or at least that push for the ready adoption of that technology for concomitant medication. So with paper we get the traditional problems of things being error prone, so people spelling things wrong or recording medication names incorrectly. This adds a burden on patients and on staff for many reasons, particularly if the patient’s handwriting is illegible or if what they’ve collected really doesn’t make sense to the site staff, you’ve got to then go back and query that. There’s also a delay in the collection of that data, so if a patient doesn’t visit a site for a number of weeks for a number of days, they will, or potentially will be collecting that concomitant medication use on paper, but they then have to pool it all together and bring it to a site, which then requires the transcription into a traditional EDC system. And that has all of the associated problems of relying on patient recall if they’ve not collected it accurately throughout the visits or between visits. And also then the fact that they’ve used a paper diary, you need to make sure that it has been recorded in time, that they’re not just filling it in before they arrive, and that the dosages are correct. This all requires more time from site staff and from the patients during their visit, and ultimately can cut down on the time that other patients have then with site staff or can prolong the duration of site visits, which isn’t something that we want in clinical trials, especially where maybe one or two sites have higher patient numbers than others. And there’s also the really key section of the delay in data collection, particularly for something like adverse events where two drugs might interact. It can really nice to have that data come through in almost real time and have it enter into your database without the need or that wait for patients, not only to arrive at the site, but also for that data to get cleaned and end up in the EDC system.
So this brings us to our next polling question. And this one is in relation to your experience. We’re wondering what your greatest challenge in collecting accurate concomitant medication information is. So I’ll leave that open for about a minute, and we’ll see how the results come through, and I’ll close it in about 60 seconds.
Okay, so you can see quite clearly there the results. Inaccurate or unreliable data and incomplete data seem to be the biggest challenges in collecting concomitant medication. And this reflects on our experience in talking to sponsors and generating data before we started to design this concomitant medication solution. So at this stage I’m going to pass over to my colleague Nora. She’s going to talk a little bit more about the benefits of using an electronic system and go through the demo of the TrialMax ConMed solution.
Great. Thank you, Karl. So as Karl mentioned, the challenges when collecting ConMeds during site visits are, amongst others, not getting always accurate or reliable data. And this is mainly due to relying on that patient recall for the whole time in between site visits, which can be several weeks. And then on top of that, it makes the site visit longer, so there’s that extra bit of burden, and any drug interaction, any results of the data is captured nowhere near real time.
So we believe that collecting concomitant medication on an electronic diary will have benefits. Apart from that increased reliability and accuracy of the data, it will add to the current benefits of the electronic COA. If the study is already using an eDiary, then that ConMed collection part can be just added onto the eDiary. And we have also seen a bit of an increase in emphasis on having that insight into what medications do the patients take during the trial, whether it’s because of exclusion criteria, possible drug interactions, as Karl mentioned, adverse events, etc. And another thing that has come to us through the sponsors and CROs has been an increase in requests from regulatory bodies, specifically asking to collect this information on an electronic diary, and we think it’s for all these reasons we have mentioned. And to summarize that, basically, it’s because the electronic diary can provide a better quality data than the traditional method.
So we have decided to create an eDiary solution to collect ConMeds, to be able to provide that accurate concomitant therapy data. But one thing that we thought is absolutely crucial for that solution to work is that it needs to be intuitive for the patients. Otherwise, patients would hesitate to use this solution to report their medications, and that of course is not the outcome that we want. The good thing though is that most of the subjects already use an eDiary to collect ePROs. So we can just add it onto their eDiary.
So when creating an eDiary solution, we took a step back and looked at all these different aspects and worked with all these different departments to get all the input first. So of course there are regulatory guidelines that need to be followed. There’s a lot of experience within the company and also kind of knowledge coming from outcomes, coming from therapeutic areas, departments, and lessons learned when deploying eCOA in global clinical trials, so all those we can draw from. And user experience has been really important when developing the solution. This is where the actual user interface—the screens and the flow—is designed, and this is what makes sure that the patients will find it easy to use, and also the usability is then tested with participants, again under user experience oversight. And there of course sponsor needs and CRO needs on the kind of data that is required and the kind of monitoring that’s also needed. So all of this input basically went into creating an eDiary solution.
And this is what we have come up with, what was the original result, called TrialMax ConMed. It basically comes in two parts—the eDiary part, this is an additional part for the eDiary, or it could be just standing on its own, where the patient reports any concomitant medication data, whether it’s a usual medication that they take regularly that they have been maybe prescribed, or anything new that they have just bought as a rescue medication over the counter, basically anything that the patient takes can be reported in that eDiary. And so then that data gets sent to our database and can be viewed in the web portal, in our case in the TrialManager, were the investigator can see what data is being reported and also, in the case of some specific scenarios, then they can also be amended.
And before I show you a quick demo of the system, so you can actually have a good idea of how that looks, I would like to talk a little bit more about the usability testing that we have done with this solution and present to you some interesting findings that we came across in that usability testing.
So this usability testing basically means that we took participants between 60 and 82 years old. And we wanted to cover the worst case scenario. So this means that we did not train these people at all on using this eDiary. We just gave it to them and said, please report this and this medication, in a few different scenarios. And then we just followed how they interacted with the eDiary and how were they reporting, what kind of mistakes, or where they got stuck, etc. Based on that of course we got a lot of feedback. Then we immediately changed the eDiary based on all that feedback. And then we showed it to them again and gave them new tasks. So this we have actually repeated three times, to make sure that the resulting eDiary is really intuitive for anyone who just picks it up without any training and anyone that is able to enter that concomitant medication that they just took.
And to show you some of the findings and some of the changes that we made based on that feedback. So the first one is related to a scenario where patients take some brand new medication that is not their usual one. So they haven’t already reported it but they want to report it now. So there is some kind of big list of medications that are maybe available in their country, and the patient needs to select which medication name that was. So originally we thought okay we’re going to make it easy for the patient, let them just enter maybe the first two letters of the medication name and then they can see, like in a dictionary, all the names starting with those letters and they will select the correct one. So we had that option first, and as a backup we had a kind of scrollable list of all medications. But we found out that actually this list, that you can see on the screen, this list of medication that you can scroll through with your finger, that was the preferred method, even for people who haven’t use a smartphone before. So actually we added a little bit of training or guidance just before that just to show everyone how the scrolling list works, that you just use your finger to scroll through it. After seeing this, everyone was able to use it and everyone actually preferred that. So now this is the primary method, just scrolling through the list. And if the patients want, they can still search by the name with that search-by-name button, and then they can type in the first few letters, but they don’t have to do that, as they can just scroll through that list and just select their medication name.
Okay, another finding, or another kind of improvement that we have done in the solution, is related to this case where the patient, after selecting the medication name, they need to enter the strength and unit of the medication. And even, you know, for someone like myself it’s not always easy to think about what exactly is meant by strength, by unit, just on top of your head, it can get mixed up easily, let alone for anyone in the general public. So we have realized that the easiest way is to combine all this information on one screen, give them this list that is populated with all the kinds of units, such as milligrams and micrograms. So once you tap on that list, all these options show up. So then it’s clear, okay, here I will select milligrams, for example, and then it gets context that on top you have to enter the strength, for example 5 500 mg.
And we have also even the option for the patient to say I don’t know the strength or the units. And in that case it’s fine, they can just select that option below, and then they don't of course have to enter that, and that information will need to be later edited by the investigator.
And after all this information is being entered into the eDiary, for that new drug that the patient is starting to report, we have realized that instead of just navigating the patient right away to the main menu or somewhere else, it’s been a good practice to say, okay you have now finished doing this task, thank you, and you can either continue with this action or you can now exit. So it’s kind of confirms to the person using the diary, okay you are done, this is fine, if you want to exit now go ahead, or you can continue. And this has actually been a big improvement to the feel for using the eDiary and the user experience.
So let me show you the demo. I also see that we have a few questions asked. So we will have a Q&A session at the end, but also you might already see some of these in the demo.
So what I’m going to do now is, I actually have an eDiary here, connected to my computer. So what you can see now is basically transmitting this screen of my eDiary that I have connected to my computer. So I’m just going to use that eDiary, and you will see the screen. So I will log in as a patient, and go ahead and report a concomitant medication. Great. So the first thing is that we allow the patient to see their recently reported medications, so that they know that they have already reported and don’t have to worry about reporting it twice or remember what’s already been done. And then there’s an option to report new medication. We have some guiding text throughout. Some people will not need them and as a result they will not read them. And that’s perfectly fine, they can just skip them. But for other users these are really useful texts guiding them throughout.
Okay, so first of all, every patient has kind of a list of their personal medications that they usually take that maybe they have at home, that have been prescribed to them, etc. And most of the time, they will take one of these medications because that’s what is accessible to them. So I’m going to show this scenario now, of our patient who has today taken two tablets of Nurofen, which is already on their list. So all I need to do is select the Nurofen and report the intake. So first of all, I will say that it has been today. And also at what time. I’m going to say 2 pm, that’s already been here in the UK, that will be accepted. And then of course the patent needs to also select the dose, so this is where we kind of distinguish between strength and the dose. The patient needs to here say that two doses have been taken.
And read this screen just to make sure that everything has been entered correctly. Okay. And here we can see that thank-you screen, so a similar one that we’ve shown also in the usability study. And if the patient continues they can go ahead and report additional medications. now you can see that Nurofen taken today is on the list of reported medications. So in order to show you those screens mentioned in the usability study findings, what I’ll do now is go into that a bit more complicated scenario, and a bit more rare scenario as well, where the patient actually needs to report medication that is not on their list yet, something completely new. So this shouldn’t be really happening that often but we need to account for that possibility. So in here, medication is not on the list, so patient will select “I took a non-listed medication.” And then we give a bit more instruction saying, okay on the next few pages, we’re going to need to know a few of these details of that new medication. We allow the patient—or we can allow the patient—to report that medication even if they didn’t know the name. But let’s say the name is known by the patient. And here is the scrollable list that I have mentioned, it maybe doesn’t relate so well on the webinar, but basically I’m just scrolling through it with my finger and it can be done as fast or as slow as you need. And I will just select some kind of medication. Okay. And this takes us to the strength and unit screen. I’ll just select 30 mg. But as I said, the patient might not actually know the strength, and it could be a bit confusion for some of them. So if they don’t know, they can tick this part and say okay strength or units not known, that’s fine as well. And then lastly just confirm that this has been taken by mouth, so these are tablets or capsules. Most of the time they are, but if not, then you ask about the alternative route. And some patients might want descriptions to their medication names, maybe they don’t remember them by their names but by their color or something else. So that description here is possible too.
All right, but I’m just going to leave that out and just add this new medication, Atasol 30, it is an oral one but strength is not known. And because I actually have reported that strength is not known, we’re just reminding patients or telling the patients to please bring the medication package to their next visit, so that this information can be added by the investigator. That’s just a quick reminder. And once that’s done, again we are just saying thank you, your new medication has been added, so you’re now done. If you took that medication, please tap “continue” so that you can report the intake of that new medication. But I’m not going to go into that now as we’ve already seen that. So at this point, I could add this, or I will just exit, but I’ll just show you that this new medication, Atasol 30 is now on the patient’s personal list as well. So anytime in the future the patient wants to report this, it’s already on their list.
Okay. So this would conclude our eDiary demo, but what I would also like to show you is how that looks on the web portal, TrialManager, so I’m going to switch to there. Great. You should be able to see that. So I don’t want to go into too many details. Of course, we can show summaries of pending items and reports, etc. I just want to show you one little thing. Choose a patient. Okay.
Just to show you how that list of patient’s personal mediations they usually take can be also viewed and managed by the investigator. So in this case, this is a slightly different patient, just for the sake of example. This patient’s personal list consists of two concomitant medications that have been already approved or maybe entered by the investigator for them, but then the patient—similarly like I did now—has added a new medication on their own. So the patient themselves entered that name, that description, and they also didn’t know the strength of that. So this is where now the investigator can go, view the details, and actually press edit, and be able to edit that strength and that unit of that medication. So I’m just going to add some made up units and strength. And now you can see that, as an investigator I have added the details. Once I confirm that in TrialManager this would be synchronized black to the patient’s eDiary, and the patient would be reporting that medication with the correct strength. So this is something that can be done maybe during the next patient visit, or the investigator could call the patient and ask what medication that is and add that missing information. So that flexibility is there.
All right. So I will stop sharing TrialManager and go back to our presentation.
So before we get to our question and answer session, I would just like to add a few more considerations. I mentioned a few of them of course. The whole system brings up many questions and many other things to consider. So just a few of those that I wanted to mention.
First of all, of course I have shown you a list of medications that a patient might choose from, and this list needs to be taken from somewhere and is country specific. So some sponsors have these lists available, have very specific lists available. But there are also databases out there that have different kinds of lists based on indication, based on how regular drugs are in each country. So these databases can be used to make these lists and make them country specific for the trial.
Another consideration is to think about for a specific study, what data do we need. Do we always need the full information—what time did the patient take, how many or what dose of the medication. Or sometimes maybe a weekly confirmation is fine for regular dose. If a patient is expected to take one pill of that pain medication every day, maybe we just want them to confirm that every day they took it in the last week or maybe on Wednesday the have missed one. So in that case, we could make the diary more simple, and the benefit of the eDiary is that it’s really flexible so that what I showed you was maybe a broader example but we can simplify it by just asking for these confirmations or regular doses or asking less information.
Coding of the medication is another important aspect, so deciding on how the medications will be coded. Is it going to be by active ingredient, are we going to add the indication there, etc. Of course, all the data will also be audit trailed, so that will be part of any kind of solution. But reconciliation is another thing that comes up, you know, as I showed, investigators can add certain information. But on the other hand, we don’t recommend that both investigators and subjects report that same thing, the ConMed usage, because then the reconciliation can get very complicated.
So these are some of the considerations. And in terms of possible future development or future expansion, we would certainly very much like to make use of bar codes so that the patient could just scan a bar code of the medication packaging and then they wouldn’t have to enter that strength and dose and name at all. It is already being used, for example, in agriculture. But it’s a little bit of a more complex problem in global studies where there are so many bar codes out there and so many products.
Making this an app to be used as a BYOD solution could be a nice idea for the future, especially if the ConMed data is not required for a primary endpoint in the study. This could be actually a good start to start using BYOD by sponsored CRO. And if we then get into apps we could also be making use of apps which recognize pills based on a picture or shape of them, and those could again help the patient identify their medication.
So this brings us to our last poll before time for questions. And this one is actually not going to be public. We just want to give you an option to let us follow up with you about TrialMax ConMed in case you have any suggestions of things to add or discuss, or if you are interested in the solution, maybe in a demo or discussing with us, that would be great. So just let us know here in the poll, and we’re not going to be showing the results.
So please enter your questions into the chat box, and we already have a few questions lined up here.
[Q&A section starts at 36:42]