Development of a Reliable, Valid, and Sensitive Outcome Measure in Rett Syndrome

Your child is being asked to take part in this research study because he or she has been diagnosed with Rett Syndrome. 

Your child does not have to be in this research study. You may choose to not allow your child to be in this study and get other treatments without changing your or your child’s healthcare, services, or other rights. Your child can stop being in this study at any time. If we learn something new that may affect the risks or benefits of this study, you will be told so that you can decide whether or not you still want your child to be in this study. Your child’s medical record will contain a note saying your child is in a research study and may contain some research information about your child. Anyone you authorize to receive your child’s medical record will also get this information. 

Although clinical trials have been completed and are ongoing in RTT, there remains a need for well validated Clinical Outcome Assessments (COA). Clinical Outcome Assessments tell us how affected your child is with Rett syndrome, and they can be used in clinical trials to see if the treatment is helping improve the clinical condition of your child. For an assessment to useful in a trial, we need to understand some aspects of the measure. For example, we need to know how stable the scores are on this measure when we look at the same person over a short period of time (1-2 weeks). This is called “test-retest” reliability because it lets us know how stable the measure is in a time period that we do not expect it to change much. We also want to make sure that when two different “raters” of the measure score the same person that the scores from these two raters are the same or close. This is called “interrater” reliability. We also want to make sure that if the same “rater” rates the same person’s exam twice, they get the same score on the measure. This is called “intra-rater” reliability. Finally, we need to know how well a new Clinical Outcome Assessment is related to other measures of similar clinical features, which is called “validity”. Finally, we need a way to train new “raters” in this new Clinical Outcome Assessment and make sure they know how to correctly and consistently score the new measure. All of these things make it so that we will be able to use this new Clinical Outcome Assessment in future multi-site clinical trials in Rett syndrome. 

The purpose of this study is to assess the reliability and validity the revised-motor behavior assessment (R-MBA) This study will involve conducting a structured clinical examination and evaluation using defined rating scales on people with Rett syndrome. The clinical examination will be video recorded to enable evaluation and rating by the same or different raters to establish reliability of the rating scales used. The videos captured will be used to develop a video-based rater training platform, as well as for future analysis to develop new rating scales in RTT.

How many participants will be enrolled in this study: 

A cohort of subjects both male and female (total n=50, n=25 per year) will be enrolled from the Vanderbilt University Medical Center (VUMC) Rett Clinic. Half of the participants (25) will be required to complete one study visit. The remaining half will be required to return to VUMC for a second study visit 2 weeks after the first visit. 

Side effects and risks that you can expect if you take part in this study: 

No invasive procedures or assessments will be performed. This study is observational in nature without administration of a treatment. There will be no withholding of normal treatments as a result of study participation. Refusal to enroll or withdrawal from this study will not affect the clinical care of your child. 

The risks to your child are minimal. One potential risk is that even though we will work to maintain your identity secret, there is the risk that of that someone will find out your identity (breach of confidentiality). All survey responses and other digital data including video recordings will be stored in a de-identified fashion on encrypted, password protected servers. Nonetheless, for all parts of this project all personnel involved with access to private health information will undergo training in Good Clinical Practice and HIPAA compliance and will follow stringent guidelines to prevent such breaches. 

The video-assessments do have a minimal theoretical risk to privacy due to recording of faces, but this risk is minimized because videos will be de-identified and transmitted directly via an encrypted interface to secure study servers which are only accessible to authorized study personnel. The video-based training platforms will include your likeness but will not include your name or any personal identifying information. 

Good effects that might result from this study: 

This is not a treatment trial, so direct participant benefits to your child are not expected. 

A potential indirect benefit to participants from this study may arise through the development of an outcome measure in treatment trials these participants might be part of in future. Ultimately, this study could benefit the Rett syndrome population by allowing us to develop effective therapeutic interventions, thus maximizing their developmental potential and enhancing quality of life. 

Procedures to be followed: 

During this study your child will undergo in-person clinical structured evaluations at VUMC including the R-MBA. These clinical evaluations will be video-taped to enable scoring by a second rater to establish inter-rater reliability, and by the same rater at a later time to establish intra-rater reliability. Additionally, these recorded videos will be used to create educational videos and video-vignettes to train potential raters. 

In addition to the structured clinical examination, your child will be assessed using established rating scales: Rett Syndrome Behavior Questionnaire (Care-giver reported, 45-item questionnaire), the Child Health Questionnaire Parent Form 50, Aberrant Behavior Checklist (Care-giver reported questionnaire, 58-items), and the Vineland Adaptive Behavior Skills assessment (Clinician-guided interview). A subset (~1/2) of the subjects will be asked to return 1-2 weeks after initial evaluation for a repeat structured clinical assessment to establish test-retest variability. 

Video Recording and Usage: 

The study visit including all assessments with your child will be video recorded for multiple purposes. The recordings will allow the research staff to reevaluate the originally assessment at a later date which will help the research staff assess the R-MBA. In addition, the recordings will be edited and used for training purposes to ensure that those using the R-MBA are using the COA correctly. Your child’s name or identifying information will not be used or released in the video recordings. Other institutions using the video recordings for training and educations purposes will not receive any identifying information about your child. However, your child’s face will be in the video and it is possible that your child could be recognized from the video recording.