A defensible comparator for the study you can’t randomize.
When patients cannot wait in a placebo arm, or the budget cannot pay for one, an external control can carry the comparison — if it is designed in from the start. Variacle helps you build it so that funders, ethics committees and industry partners take it seriously — and, when your hospital is the sponsor, takes care of the regulatory submission.
| 1:1 randomized | 3:1 + external control | |
|---|---|---|
| Patients on the new treatment | 50% | 75% |
| Information on the control outcome | Concurrent arm only | Concurrent arm and external cohort |
| What limits precision | Size of the control arm | Quality of the external data and its assumptions |
When a full control arm is not an option.
No standard of care to compare against
Last-line and advanced therapies, where the ethics committee will not allow the innovative treatment to be withheld.
Small populations
Rare and paediatric diseases, where a full control arm would take years to recruit.
A new therapy with small, uncontrolled studies
Promising early results, an ethical objection to a large placebo arm, and no budget for a large trial.
Reviewers said “the data are unbalanced”
And suggested matching that throws most of your patients away.
Investigator-initiated trial? We handle the regulatory side.
In an investigator-initiated trial the hospital is the legal sponsor, the investigator is the principal investigator, and the drug often belongs to a company. Most hospitals have no regulatory team. We prepare the application, submit it through CTIS and keep the regulators' clock.
The scientific dossier
- Protocol, with the statistical methods: sample size, comparator, analysis, missing data
- Statistical analysis plan
- Investigator's brochure, product quality dossier and labelling, coordinated with the company that supplies the drug
- Scientific advice and low-intervention status, where they apply
The national dossier
- Patient information and informed consent, in the local language
- Recruitment arrangements
- Suitability of each investigator and site
- Insurance, financial arrangements and data protection
From upload to decision
- Submission through CTIS with a role delegated by the sponsor; legal responsibility stays with the hospital
- Answers to the regulators' requests for information within the 12-day deadline
- A one-page split of responsibilities between hospital and company, agreed before anything is submitted
- Coordination with the CRO that monitors the trial at your site
Methods you can defend, written for the people who decide.
We work alongside your team and your hospital's research unit, from the first sketch of the design to the reviewers' last question.
Design and sample size
Single arm with an external control, or unbalanced randomization (for example 3:1) that keeps a small concurrent control to anchor the comparison. Power is computed with the external information included.
Protocol, SAP and ethics-committee annex
Estimands per ICH E9(R1), the identifying assumptions, the estimation method and a sensitivity analysis — written so that a committee can follow them.
Funding applications
Methodology sections for competitive public calls and for industry programmes that fund investigator-initiated trials.
Re-analysis for resubmission
Efficient estimation on the full sample instead of discarding data, external data to strengthen sparse groups, and a sensitivity analysis reviewers can check.
A stronger proposal with much less risk.
Industry partners and funders back risk they can see. “Promising single-arm results” is a hard sell; a pre-specified comparator with stated assumptions and a sensitivity analysis is a value proposition they can evaluate.
The same work protects you later. When the comparison is fixed before outcomes are seen, a reviewer cannot dismiss the result as an artefact of the analysis — and if the treatment does not work, you learn that honestly.
Your therapy may well work. What you are missing is a comparator the committee will accept.
What investigators ask us.
Is a study with an external control publishable?
Where would the external data come from?
Can we add an external control to a study that is already running?
When should we contact you?
Can you do the submission in CTIS for our hospital?
Who is responsible when the hospital sponsors and a company owns the drug?
Can we talk before sharing anything confidential?
Tell us about the study you want to run.
A 30-minute conversation about your design. We will tell you honestly whether an external control helps — and if it does not, what would.