Skip to content
For CROs

Add external controls to your offer — without building a department.

Sponsors increasingly want to know, before the protocol, what evidence the regulator and the payer will need. Variacle gives your team that answer and delivers the external-control module inside your project: your client relationship and contract, our method and deliverables.

Discuss a proposal moduleWhat we deliver
Phase-2 proposal · comparator optionIllustrative
DesignControls to recruit
Standard 1:1 randomization120
2:1 randomization, augmented with external controls60
Single arm with a pre-specified external control0
Options your BD team can put in front of a sponsor, each with its regulatory risk stated. The final design is sized on the sponsor's data in step two.
What your team gets

More to sell in the phase‑2 conversation, less to staff.

Phase 2 is where sponsors decide what evidence they will need for the regulator, the payer and a possible partner. It is also the last moment an external control can be designed in.

A reason to open the conversation

For a given indication: how many comparable historical control patients exist, how much smaller the control arm could plausibly be, and which precedents support it — from public sources, before any data changes hands.

A capability you don’t have to build

Identification, transport between populations and assumption-indexed sensitivity analysis, written in the estimand language of ICH E9(R1). Most mid-sized CROs cannot offer this in-house.

One extraction, not three

Outcome definitions and the data specification are fixed before the first pull, and the extraction runs in a reproducible pipeline: fewer project weeks, less re-work.

Documents that go into the dossier

Statistical analysis plan sections, estimand statements, statistical reports and the sensitivity package; medical writing with a partner.

How we work with you

A module in your proposal, then a step in your process.

Inside your project

We work under your project management and your contract.

Priced as a module

A fixed fee per step, sized to sit comfortably within the study budget you present to the sponsor.

Early, because it has to be

An external control cannot be added mid-study. We join the design conversation — exactly where your BD team wants to be.

From one study to a process

The goal is an evidence-planning step in every phase‑2 conversation, not a one-off per study.

The module

Four steps your proposal can include.

  1. 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
  2. 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
  3. STEP 03

    Protocol and submission

    The statistical sections of the protocol and the analysis plan, written to sit inside your study documents. The CTIS submission stays with your regulatory team; we cover it only where your team does not.

    DeliverableProtocol statistics and SAP
  4. 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 the module delivers

What your sponsor receives, under your project.

Your team keeps the client relationship; the module adds the external-control analysis and the documents behind it.

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
Vendor qualification

Built for your supplier questionnaire.

As a sub-processor we add as little friction as possible to your audit: patient-level data stays under your control, and every deliverable is traceable.

Data stays where it is

Where patient-level data cannot move, the analysis goes to it: a versioned package that runs inside your environment, or your data partner's, and returns aggregates only.

Reproducible by construction

Versioned code, checksummed inputs and independent double programming. Every number in a report can be regenerated and traced to its source.

Documented quality system

SOPs for deliverable review and approval, change control, data protection and business continuity, aligned with ISO 9001 principles and with ICH E6(R3) where it applies to our role.

Contracts that fit your MSA

GDPR data processing agreements and documented technical and organisational measures that slot into your vendor framework and supplier questionnaire.

Questions

What CRO teams ask us.

Who owns the client relationship?
You do. We work inside your project and your contract with the sponsor, and we join sponsor meetings when you want the method defended in the room.
Do you compete with our regulatory team?
No. Submissions are your business. We prepare the statistical sections your dossier needs, and handle the CTIS submission only where your team does not cover it — for example for a sponsor with no regulatory staff of its own.
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 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.
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.
How is it priced?
A fixed fee per step, agreed before each step starts and sized as a fraction of what the alternative study would cost. You decide at the end of each step whether to continue. The first conversation is free.

Bring external controls into your next phase‑2 proposal.

A 30-minute call with your BD or RWE lead: where the module fits in your offer, what it costs and what we need from you.

Book a call