Natural history studies (NHS) gather information about how a disease or condition affects a person over their lifetime. This can include their symptoms (severity and age of onset), diagnosis (how and when), medications (efficacy and side effects), and even quality of life. NHS can use data created by clinicians or by patients/caregivers, or a combination of both.

NHS provide crucial information about a disorder. This includes:

• Understanding of the disorder

• • Catalog symptoms 

  • Catalog treatments

  • Record quality of life 

  • Genotype-phenotype correlations

  • Who is at risk for particular symptoms

  • Understand factors contributing to symptom severity

  • Data to develop standards of care

• Time-line of the disorder

• • When symptoms start

  • How fast those symptoms may change

  • Optimal treatment window to prevent symptoms

• Measuring change

• • Test new outcome measures

  • Determine treatment effectiveness

  • Correlate biomarkers with prognosis

  • Create a natural control group

NHS are very important for clinical trials. In order to design an effective clinical trial, a pharmaceutical or biotechnology company will want to know:

• What symptoms to target

• What age groups to include

• How quickly they will know if their treatment is working

• What outcome measures accurately detect these changes

• Particular types of patients (certain symptoms, specific variants, etc.)

At COMBINEDBrain, we collect natural history data on a platform called Matrix, operated by Across Healthcare, a health data company. Matrix is designed to be used for regulatory approval, being fully-auditable and compliant with HIPAA, GDPR, and FDA 21 CFR Part 11. Data can be entered by patients/caregivers and by clinicians. Data can be in the form of survey responses, customized symptom trackers, electronic health record (EHR) integration, or document upload. Supported documents include genetic reports, lab tests, guardianship documents, and raw EEGs.

Log into your PAG’s Matrix portal

Validated surveys collected on Matrix

For neurodevelopmental disorders:

• ClinGen GenomeConnect head-to-toe surveys

• Vineland Adaptive Behavior Scales 3

• PELHS Seizure Survey

• CDC Milestone Survey

• Observer-Reported Communication Ability (ORCA)

• Aberrant Behavior Checklist-Community (ABC-C)

• NICHQ Vanderbilt ADHD Assessment Scale

• Nisonger Child Behavior Rating Form (NCBRF)

• Children’s Sleep Habits Questionnaire (CSHQ)

• Quality of Life Inventory - Disability (QI-Disability)

For adult-onset neurological disorders:

• ClinGen GenomeConnect head-to-toe surveys

• Neuro-QoL - Cognitive Function (Item Bank)

• Neuro-QoL - Lower Extremity Function - Mobility (Item Bank)

Clinician-entered surveys:

• Scale for the Assessment and Rating of Ataxia (SARA)

• Burke–Fahn–Marsden Dystonia Rating Scale

• Clinical Global Impression of Change (CGI) 

Researchers: Access Matrix data

We share data to all types of researchers, whether they are associated with academia, industry, or non-profits. In order to access Matrix data, please contact sarah@combinedbrain.org or studies@combinedbrain.org. The data use agreement can be previewed here: Matrix Data Transfer and Use Agreement.

FAQ

How is a natural history study different from a registry?

A registry is a single point in time and often prioritizes demographics, contact information, and current symptoms. A NHS is longitudinal, meaning data are collected from the same participant multiple times. This allows us to learn the trajectory of the disorder.

How does our natural history study relate to the biorepository?

Participants consent for the biorepository on Matrix, our NHS platform. Using an anonymous linker ID (the Clinical Research ID), we pair their biosamples to information they provide in Matrix about their symptoms, milestones, and medications. Pairing this information to biosamples can be used to develop biomarkers.

I want to learn more about using Matrix

Our Director of Natural History leads a twice-monthly call, demonstrating in depth various features of the Matrix platform, as well as allowing for open discussion and Q&A. This call is open to any researcher, clinician, or PAG representative who is interested in learning more about Matrix, regardless of whether your community is already using the platform or not. Email sarah@combinedbrain.org to be added to the calendar invitation.

How do participants sign up?

• Adult PATIENTS (or CARRIERS of the disorder)

• CAREGIVERS enrolling a CHILD PARTICIPANT (minor child, adult child not able to consent)

• Adult UNAFFECTED FAMILY MEMBERS enrolling as an unaffected control participant

I need help logging in

Please contact studies@combinedbrain.org.