David Lieberman, MD, PhD: There are a few outcome measures, such as the RSBQ and the CGI-severity scale or CGI-improvements scale, that are currently used in in clinical trials. RSBQ stands for Rett syndrome behavior questionnaire, and that is one that’s completed by the caregiver. [It] asks several questions that give you some information across 8 areas. CGI stands for clinical global impression, and you can either have an impression of severity and a separate impression of improvement, and the clinical global impression of severity is a 7-point scale from unaffected to severely affected. That is a clinician-rated scale that could be used in the clinic, and we are using them for some natural history study on data. I don’t feel that they’re all that helpful in clinical practice, because I don’t necessarily need to tabulate numbers across several behavior components. I focus on what issues the parents have when I’m having a clinic visit with them. We may focus on a few issues at a time. The RSBQ was intended originally as a way to help differentiate patients with Rett syndrome who might be at an institution, a facility for those with intellectual disability, let’s say, and how Rett syndrome patients would appear different than others. The higher the score, the more Rett-like they are. It was never really intended as a clinical outcome measure. I think there are some flaws with that approach. Right now, that’s the best we have. I know there are groups trying to work on improved outcome measures for clinical trials. Some of those may involve devices and biosensors that could provide more objective data. As I said, some of the symptoms present in Rett syndrome that we try to treat could be breath-holding and hyperventilation. That might be very difficult for parents to keep track of on an hour-to-hour or day-to-day basis. When you have a device that could measure breathing; you could get a quantitative assessment of that measure and follow it over time. There’s bound to be more clinical measures for Rett in the future.

There are some other measures that we could use in the clinic. There’s an ATOMS [Altered Transfer of Momentary Mental States] scale that helps to look at mood disorders that can be completed by the caregiver. Some may find that helpful. Again, I think just the discussion with the parents about their child can get at the meat of the issue. We do our initial assessments based on just history and physical, and I think that’s the same as what most clinicians would be doing.

One of the things that I think is hard to assess is communication. If you ask parents what are some of the things they want to see improving in their kids, it’s among the top 3 or 4, with other ones being improvement in their seizures and improvement in their ambulation. Communication is up there. Most girls and women and boys with Rett are nonverbal. They can communicate using eye gaze, because they don’t have hand function that they could use to either create signs or to activate icons on a computer screen, for example. With eye gaze, their gaze kind of functions as a computer mouse, and they can make selections that way. They can put words and sentences together. What makes it difficult is each girl has her own personalized screens on her communication device. It would be hard to implement a standardized assessment of that. There are some other ways that that this measure has been helpful…there’s a Mullen scale of development that can help ascertain some cognitive capacity. There’ve been publications that showed that using this kind of eye gaze device in a modified way can get more appropriate responses from the individual than if that device is not used. I think there’s a lot of room for trying to come up with tools to assess communication. I think that’ll be helpful for future clinical trials.

Transcript edited for clarity.