Your completed trials already hold the control arm you need.
Placebo and standard-of-care arms from finished studies are the strongest external control there is: randomized, measured to protocol, already paid for. Variacle turns them — with the real-world data you can access — into a pre-specified comparator for your next study, and defends it with you in front of the regulator.
Assumed bias δ = 0.20beyond the tipping point+0.6 (-0.7–+1.9)
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← Favours controlFavours treatment →
The conclusion holds until the external comparison is biased by δ ≈ 0.16 on the restricted-mean-survival-time scale — a magnitude your clinicians can judge.
What changes for you
Less recruitment, a stronger dossier, an answer for the payer.
Fewer control patients
Shrink or replace the concurrent control arm where the external comparator is strong enough. The size of the reduction is simulated before you commit, not promised.
A comparator the regulator can follow
Estimand, time zero, eligibility emulation and sensitivity analyses aligned with ICH E9(R1) and the FDA guidance on externally controlled trials.
Evidence that also serves HTA
The same comparator supports payer and HTA submissions, where single-arm evidence often stalls after approval.
Before you sign
The four questions every sponsor asks, answered before the contract.
01How many control patients do I save?
02How much time do I gain?
03How much regulatory risk do I take on, or remove?
04What is my net gain?
Whether an external control pays off depends on what already exists in your indication: how many controlled trials, with which endpoints and sample sizes, and what the regulator has accepted before. Most of that is public. We map it and give you a range with its assumptions written down — an estimate, not a promise. The real answer comes from your data in step two.
Who it is for
Each function gets something it can measure.
Clinical development or real-world evidence? Both. The efficacy question, and the budget, belong to clinical development; the data usually sits with the RWE team. We turn observational data into trial-grade evidence, so we work with both.
RoleWhat changes
Clinical study directorApproval sooner, with fewer patients exposed to placebo.
Head of biometricsYour team keeps the primary analysis; we add an identification argument and a sensitivity package the agency can audit.
Regulatory affairsGo to scientific advice with a written synopsis, and to CTIS with a complete dossier.
Market access and HEORA comparator built for the payer as well as the regulator.
Clinical operationsFewer control patients to recruit, retain and pay for.
Real-world evidence teamsAn efficacy-grade use for the data you already curate, inside a development programme.
Where it fits
Designed for the studies a randomized control cannot serve.
Not to replace randomized trials where they are feasible: to make evidence possible where they are not.
Single-arm studies
No concurrent control, or one too small to stand alone.
Advanced therapies and last-line oncology
Where ethics committees will not allow the innovative treatment to be withheld.
Rare and paediatric diseases
Where a full control arm would take years to recruit.
Hybrid designs
Augment a small randomized control with external patients, under explicit borrowing rules.
Completed and negative trials
Control arms that already cost you money to store, put back to work.
Two safe ways to start
Test the method without putting a submission at risk.
A new methodology should never be the single point of failure of a pivotal programme. These two entry points let your teams and the agency see it work first.
Retrospective
On a closed trial
Use a finished study as a sandbox. We rebuild the comparison with external data and show what the method recovers against the randomized answer you already know — with nothing at stake for an ongoing submission.
Prospective
On a new trial, as a secondary analysis
Pre-specify the external-control analysis in the statistical analysis plan as secondary or exploratory, alongside the standard design. The agency sees the method; your study does not depend on it.
How an engagement runs
Fixed scope, fixed fee, a decision at every step.
STEP 01
Scientific advice
Before the protocol is written: a short synopsis of the design, the data and the method, ready for scientific advice with the EMA, a national agency or the FDA. You learn whether the regulator will follow before you commit.
DeliverableSynopsis and briefing materials
STEP 02
Feasibility and design
We audit the data you hold or can access, and the data your study will collect: comparability, endpoints, time zero, missing data and sources of bias. If an external control is not viable for your question, this step says so in writing.
DeliverableReport with risks and red flags, proposed design and a simulation of the final analysis
STEP 03
Protocol and submission
The statistical sections of the protocol and the analysis plan. If you have no regulatory team, the full Part I and Part II dossier, submitted through CTIS on your behalf, with the regulators' questions answered on time.
DeliverableProtocol statistics, SAP and, where needed, the CTIS application
STEP 04
Pre-specified analysis
The analysis runs as planned, alongside your study, with a sensitivity analysis for every identifying assumption and the documentation trail the dossier needs.
DeliverableStatistical report and regulatory package
Optional modules: sourcing and access requests for external data, and medical writing with a partner.
What it looks like
A sponsor's own placebo arms, transported to a new study.
What the work looks likeTypical project
External historical control for a single-arm study
The comparator is built from the placebo arms of a sponsor's own completed randomized trials and transported to the population of the new study. Evidence already paid for, put back to work.
What you receive
Estimands written to ICH E9(R1), with every identifying assumption stated one by one
A sensitivity analysis for each assumption, relaxed one at a time, with its tipping point and E-values
Independent double programming of every derived quantity
A reproducible package: versioned code and checksummed inputs, so every reported number can be regenerated
Questions
Objections we expect, and our answers.
Our biostatistics team already does this. Why add you?
We do not replace them. Your team keeps the primary analysis; we add the identification argument, the register of assumptions and the sensitivity package — the parts that are hardest to certify from inside. Sharper, not substituted.
Will a regulator accept an external control?
When randomization is not feasible or not ethical, regulators have accepted external comparators as pivotal or supportive evidence. Acceptance depends on process: the comparator, time zero and the analysis plan fixed in advance, and sensitivity analyses that show how robust the conclusion is. That is why we start with scientific advice, so you know where the agency stands before you commit.
Can you handle the regulatory submission in CTIS?
Yes, for sponsors without a regulatory team — including hospitals that sponsor investigator-initiated trials and small biotechs. We prepare Part I (protocol, statistical methods, comparator) and Part II (informed consent, sites, insurance, financial arrangements, data protection), submit through CTIS with a role delegated by the sponsor, and answer the regulators' requests for information within the 12-day deadline. Legal responsibility stays with the sponsor, as the EU Clinical Trials Regulation requires.
Do you take part in meetings with the FDA or the EMA?
Yes, alongside the sponsor, who requests and leads the meeting. We prepare the statistical case — design, estimand, external data and sensitivity analyses — and answer the methodological questions in the room.
Can we add an external control to a study that is already running?
Not as confirmatory evidence: an external control has to be pre-specified. For a running or closed study we can run a retrospective or exploratory analysis. It shows what your data could support next time, without touching the current submission.
What happens if the study is negative?
Method and result are kept apart. The estimand, the assumptions and the tipping points are fixed and dated before outcomes are seen, and the risks are flagged in writing at the start. A negative result is then a finding about the treatment, not an artefact of the comparator.
Do you provide the data?
We are a methods company, not a data vendor. We work with data you own or can access — completed trials, registries, real-world cohorts. When external data is needed, we find suitable sources and handle the access requests.
Can we talk before sharing anything confidential?
Yes. The first call needs no data. We are happy to sign your NDA before we see protocols or datasets.
How much of your next control arm do you already own?
A 30-minute call to look at your indication, the data you hold and what regulators have accepted. No data needed; NDA on request.