Information for this article was contributed by Kristen Snipes, a Project Director at Rho with extensive experience managing attention deficit hyperactivity disorder (ADHD) trials, including the recent successful completion of a phase III laboratory classroom study.
1. Selection of a clinically meaningful endpoint is critical.
I’ve found that at the beginning of a study a lot of time is spent deciding what rating scale will be used, and yet not nearly enough time is spent determining what the precise endpoint will be. Particularly in a study that will be used as part of a marketing application, defining a clinically meaningful primary end point can mean the difference between success and failure. Picking the best end point requires consulting with key opinion leaders, regulatory experts, statisticians, and a medical director experienced in clinical trials. Depending on the phase of development, a special protocol assessment with FDA may be advisable.
2. Use of online ADHD assessment tools can reduce stress on parents and sites while increasing data quality.
Using an online assessment tool, parents are able to complete assessments on their own time and don’t have to worry about getting paper assessment forms returned to the site. Making things easier for parents prevents drop-outs, which can cause timeline delays and data issues. Sites’ efforts are reduced because they don’t have to follow up with parents to get the forms, scoring is completed automatically by the system reducing variability in data and they don’t have to transcribe the data from the forms into an electronic data capture (EDC) system. This removes the possibility of data entry errors leading to higher quality data.
3. When conducting laboratory classroom studies, short visit windows may create scheduling headaches that must be carefully managed.
The laboratory classroom portion of the study typically is conducted on a Saturday. If you have a two day visit window around the classroom day, the visit must occur between Thursday and Monday. This often means the visit must occur on Thursday, Friday, or Monday. Taking into account school and work schedules, this can create a stressful situation for parents. In some cases, a narrow visit window can’t be avoided. If so, you must stay on top of this issue to avoid both protocol deviations for visits outside the window and drop-outs because parents can’t make it to the visits.
4. Use of centralized, experienced sites will help you stay on schedule.
Ideally, you want to use sites with experience in ADHD trials and EDC that have a proven track record on both patient enrollment and data quality. Sites with prior experience on ADHD trials know what it takes to enroll subjects with this indication. They will have some ideas about what type and how much advertising is needed and how to incentivize parents to participate (e.g. providing snacks for after school study visits). They also are better able to estimate how many patients they can enroll and how quickly. Conversely, delays in enrollment typical of new sites can be costly and will lead to delays in the overall timeline.
Training and consistency are keys for the laboratory classroom studies which utilize raters to assess frequency of behavior. You need to ensure that the sites are rating in a similar manner to ensure reduced variability by center. Holding a study-wide training may be more expensive but will be worth the money spent when your final analysis is complete.
It is also important to select sites with a proven track record of delivering high quality data. Experience with EDC is an important factor here. Poor data quality can increase costs by driving up the number of queries and the time spent on site resolving problems. Data quality also can delay timelines as additional effort may be necessary to clean the data prior to database lock.
5. Patient diaries aren’t all they are cracked up to be.
We see a lot of interest in using patient diaries to collect information for ADHD studies. Patient diaries allow collection of information at any time directly from patients. It sounds like a great idea; however, what you usually end up with is a lot of dirty data. It can be very difficult to draw meaningful conclusions from what you have, but once you have it, you will have to do something to address it.
When collecting dosing information, keep in mind what you plan to use it for in your analysis. Is your goal strictly compliance? If so, can you gather this from your accountability records or number of tablets returned? Reducing the burden on patients and sites helps to ensure useful, qualify data that can tell the story you want in your clinical study report (CSR).