Study design · Natural historyUpdated September 28, 2026

Natural history study software built for regulatory-grade data

Natural history data may one day define your endpoints or serve as an external comparator. Capture collects it with the same controls as a trial: structured assessments, caregiver reports, remote questionnaires and a complete audit trail over years.

  • Years of follow-up
  • Clinician, caregiver and patient data
  • Trial-grade audit trail

Free sandbox · No credit card · 21 CFR Part 11 aligned

Natural history study · 5-year schedule
AssessmentBLM6Y1Y2Y3Y4Y5
Clinical assessment
Functional scale
Caregiver reportQQQQQQ
Patient questionnaireQQQQQQ
Biomarker sample

Q = quarterly remote questionnaires between visits

Visits plus remote data in one record

What natural history studies need

  • Consistency over years: the same assessments, administered the same way, so change over time reflects the disease, not the method.
  • Several data sources: clinician assessments, caregiver observations (often in paediatric rare disease), patient questionnaires and biomarkers.
  • Low burden to keep families engaged, which usually means remote questionnaires between visits.
  • Regulatory-grade quality if the data may support endpoint selection or external control comparisons. FDA has issued guidance on natural history studies for rare disease drug development.
  • Definitions, versions and changes documented, so the dataset can be understood long after it was collected.

Data quality

Collect it like trial data, because it may become trial data

Natural history studies are observational, and they are sometimes run with lighter systems than interventional trials: spreadsheets, survey tools or registries without audit trails. That can be a costly shortcut. If the data later informs a regulatory submission, reviewers will ask how it was collected, whether definitions changed, who entered and changed values, and how complete it is. A dataset that cannot answer those questions has limited value as evidence.

Using a trial-grade system from the start costs little more. In Capture every value has a field-level audit trail, approved forms are locked and versioned, edit checks raise queries at entry, and exports include a data dictionary and annotated CRF. See the natural history study glossary entry for how these studies fit into development programmes.

Caregivers and families

Many rare diseases affect children, and much of the meaningful information comes from parents: sleep, feeding, seizures, behaviour, daily function. Assessments can be set to be completed by a caregiver on their own phone, alongside clinician-rated forms completed at visits. See the parent proxy ePRO template.

PRO

Patient-reported

Participant, own phone

ObsRO

Observer-reported

Caregiver

ClinRO

Clinician-reported

Site staff, clinic tablet

PerfO

Performance outcome

Site-run test, e.g. chair rise

Long schedules

Visits and remote questionnaires on one timeline

Visits anchored to baseline, recurring questionnaires between them, and windows and reminders that keep a years-long schedule on track. The status overview shows every participant against every visit, and the dashboard flags participants falling behind.

  • Visit anchors, windows and epochs.
  • Recurring ePRO between visits.
  • eConsent records in the same study.
EDC for registry studies
Daily evening diary · Visit 1 to Visit 15
Recurring diaryDaily18:00 to 24:00Hard window
D1✓
D2✓
D3✓
D4✓
D5✓
D6Missed
D7✓
D8✓
D9✓
D10✓
D11✓
D12✓
D13Open
D14
Compliance, last 14 days92%

Model a five-year natural history schedule

Build visits and remote questionnaires in the free sandbox.

Build your natural history study free

Study build

Natural history study checklist

Assessments fixed and versioned

Instrument versions and administration methods written down.

Definitions documented

Disease milestones and events defined in the protocol.

Caregiver roles set up

Who completes which assessment, by age.

Consent covers future use

Including possible regulatory use of the data.

Retention plan

Remote questionnaires and reminders between visits.

Data standards

CDASH-style forms and a data dictionary for later use.

Later use

Questions regulators ask of natural history data, and what answers them

QuestionWhat answers it
Were assessments done the same way throughout?Locked, versioned forms and a record of every form change and when it took effect.
Who entered and changed each value?A field-level audit trail with user, time, old and new value and reason.
How complete is the dataset?Visit and questionnaire completion by participant, with reasons for missed assessments.
How were events defined?Protocol definitions reflected in structured fields, not free text.
Is the population comparable to the trial?Eligibility-relevant characteristics captured at baseline in structured form.
Can the data be traced to source?Source documents at sites and SDV on critical fields.

Endpoint development

Using natural history data to choose trial endpoints

In rare diseases, natural history studies often show which measures change meaningfully over a realistic trial duration and which are too noisy or too slow. That makes them the evidence base for endpoint selection and for sample size assumptions in the pivotal trial. To serve that purpose, collect candidate measures at consistent intervals, record assessor and administration conditions, and capture caregiver and patient views of what matters, so the chosen endpoint can be linked to meaningful change. See clinical trial endpoints.

FAQ

Questions teams ask before they switch

Something not covered here? Ask us directly.

What software is used for natural history studies?

Ideally the same kind of validated data capture system used for trials, so the data can support regulatory use later.

Can caregivers complete assessments?

Yes. Assessments can be set to be completed by a caregiver on their own phone.

Can natural history data be used as an external control?

In some circumstances. Suitability depends on data quality and comparability, and should be discussed with regulators.

How long do natural history studies run?

Often several years. Long schedules with remote questionnaires help retention.

Can I try it free?

Yes, in the free sandbox.

Natural history data you can build on

Trial-grade controls for observational studies. Free sandbox.

Build your natural history study free