This is the final part in the 4-part series written following a Q&A session with Dr. John Harrison. During our conversation with Dr. Harrison we discussed the current problems with Alzheimer's Clinical Trials and the reasons behind the very low success rates for treatments. We then talked about some of the better instruments that can be used and how technology will help to turn the situation around in the future.
Part IV: Technology Advancements in Alzheimer's Trials
Q: As you look toward the future, what do you see as the most promising advances in terms of improving the efficiency and quality of clinical drug trials for Alzheimer’s?
Harrison: For my money, technology is where the action should be. We can use technology to parse data and detect improbable values, and it can lead to better testing and lighten the burden for raters. Simply having an electronic tablet, as opposed to fumbling around with objects and instruction manuals during testing, is a significant improvement. It can help improve quality by providing ready and easy access to test and scale content. For example, in these tests it’s important to stick initially to the manual for administration purposes. If you have the test on an iPad and an administration questions arises, only a simple click is necessary to instantly get direction, as opposed to leafing through a manual searching for guidance.
Q: What are the most promising technology advancements that are emerging?
Harrison: I think what has significant potential is new technology that provides what I call ‘unobtrusive surveillance’. This is an area I have been working on with CRF Health. Even the best raters make mistakes, and this unobtrusive surveillance can help assure integrity of testing and quality of data. It is a simple algorithm that you build into the electronic data capture. The program parses the data and improbable values are detected and reported so that you can investigate them. There are also a good number of computer assisted tests being introduced into clinical drug trials, many of which capture data directly instead of the data having to be keyed in, with the possible errors that this introduces into the process. Moving toward a fully electronic approach in which the data is essentially untouched by human hands, promises considerably greater reliability.
Q: How might technology help from the perspective of administering tests?
Harrison: There is a test of executive skills and working memory that I like to use in drug trials in which a rater says “I am going to give you one minute to give me as many examples of a category as you can think of without repeating yourself. The category is animals, begin.” Currently the rater hits the stopwatch, writes down what is said, clicks the stopwatch again after one minute and counts the number of correct responses, excluding repetitions and errors. Imagine a scenario in which a laptop or some type of digital media device is present, detects me giving the instructions, captures everything the patient says, controls the stopwatch, and parses data to score the test. That is a substantial saving of time for the rater and assures more accurate data. A good natural language processing program, with automatic scoring and assessment could lead to better drug development.
Q: From the patient perspective, do you see significant benefits being derived through technology?
Harrison: Yes. I think it can benefit patients and at the same time get better results. The most obvious benefit with computerization is time saving. With a good computerized assessment of cognition I can capture the breadth of what I think is important in 20 to 30 minutes. With traditional cognitive psychological tests you are looking at an hour, or as much as an hour and a half, to achieve the same thing. This goes beyond mere time saving. A moderately afflicted Alzheimer’s patient knows his cognition is not good and knows he is not likely to perform well. Over the course of an hour or more he or she is likely to become progressively fatigued, and it becomes increasingly challenging to conduct an effective assessment. If we can reduce the administration time of a test, we will probably maximize the quality of data as well.
Q: So then do you think the biggest benefit of using eCOA for Alzheimer’s Disease testing is time saving?
Harrison: As I mentioned, I think time saving is a significant benefit when it comes to eCOA. Experience suggests that if you get people to do outcome measures on computers they can complete them in about half the time it would if you give them paper and pencil tests. A lot of that has to do with the ease of facilitation with eCOA. Part of the challenge of getting tests done quickly is getting the equipment and materials out and prepared for the tests. That process could be eliminated with an electronic version. Also, Alzheimer’s patients are often very easily fatigued. Time saving often means money saving, but in the context of what we are doing with Alzheimer’s disease, time saving also means you are getting more meaningful data from the patient, and that is an important consideration. So beyond opportunity for time saving, I think the biggest benefits are for data capture and monitoring, and test administration efficiency.
Q: In your opinion, will eCOA reduce the burden on caregivers?
Harrison: In terms of the caregivers, there is much that could be expedited and better facilitated through eCOA. With current testing, a caregiver shows up and gets a stack of papers and someone sitting there to help fill them out. It’s a long, tedious process. A better approach would be to have instructions and forms delivered electronically to caregivers so they could complete them prior to the actual testing date. Currently, a rater has to read questions to the caregiver regarding the frequency and severity of the symptoms the patient is experiencing. It certainly would be much easier to have an electronic version of this so the caregiver could read through these scenarios on an electronic device rather than have someone read to them on site. Also, one of the things that is troublesome in Alzheimer’s disease trials is that individual visits can run over as much as two days. Much of that time is spent having caregivers rate their burden and the patient’s psychiatric condition. We’ve never tried it, but it would seem perfectly reasonable that the caregiver could do that at home prior to the on-site visit. Thus there are potentially significant advantages to using eCOA as a means to reduce the burden on caregivers.
Q: What is the importance of measuring constructional elements? And how might this be assessed electronically?
Harrison: I think measuring constructional elements has been, and will continue to be, an important aspect of assessing and measuring patient capability and the progression of Alzheimer’s disease. A lot of what we do with these tests is to have patients manipulating objects or engaged in drawing, and this is an area in which I think there could be significant advantages to administering the test electronically. For example, with certain tests we ask patients to copy a figure. I can imagine a scenario in which a patient completes the drawing on an electronic touch screen and then you would have an algorithm by which it could be scored. We might not be quite there yet with the technology, but once we are it will lead to more accuracy, and certainly make life a lot easier for everyone involved.
Q: So when you reflect on the current state of clinical drug trial testing for Alzheimer’s what is your perspective on the potential for future improvements?
Harrison: Well, certainly the current system is not optimal but even with the parameters we are working within we can improve things with high quality raters, a move toward better tests, and technology advancements. Ultimately we could make very real and significant progress through more collaboration. It would be much easier to achieve better results if a dozen or more major pharma companies got around the table in an attempt to get this fixed. I think all stakeholders would benefit so I would include site administrators and regulators at that table. This is all very achievable. If someone in a position of power came with a clear agenda to fix things, we could get to a much better place in a relatively short period of time.
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