RWE Methods · Synthetic Controls
Synthetic Control Arms
A synthetic control arm builds a comparator from patient-level real-world data, statistically matched to the treated group so a single-arm trial reads as if it were controlled.
Synthetic controls, and the matching methods behind them, are on the agenda at RWE Connect 2026 in Boston.
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What defines it
What Makes a Control “Synthetic”
A synthetic control is more than a comparison group pulled from other data. It is engineered, patient by patient, to resemble the treated arm.
The refinement
Historical vs Synthetic Control
A synthetic control is a more rigorous cousin of the historical control. Both look outside the trial; only one is matched at the patient level.
Historical Control
- Uses a whole prior cohort
- Often unadjusted for differences
- Coarse, group-level comparison
- Simple to assemble
Synthetic Control
- Matched at the patient level
- Covariates balanced by design
- Emulates a randomized arm
- Method-intensive and rigorous
A synthetic control is a type of external control arm. See also comparative effectiveness research.
How it works
How a Synthetic Control Arm Is Built
Building a synthetic control is a disciplined sequence, from the trial it emulates to the matched comparison.
The statistical toolkit
Matching Methods
The credibility of a synthetic control rests on how patients are matched or weighted. These are the core techniques, and topics of debate at RWE Connect 2026.
Getting it right
Keeping Synthetic Controls Credible
Matching is only convincing when the assumptions behind it are tested and reported. These are the essentials.
The direction of travel
Where Synthetic Controls Are Heading in 2026
Synthetic comparators are moving into the mainstream of evidence generation. These are the shifts on the agenda at RWE Connect 2026.
Who is in the room
Who Attends RWE Connect 2026
A senior, focused audience of the people who design comparators and defend the methods behind them.
Seniority is confirmed: 150+ attendees, around 60% at Director or VP level and above. The functional mix shown is indicative; confirmed registration splits are shared with sponsors from the live delegate list.
Explore
Explore Related Methods
Synthetic control arms sit within a wider RWE methods toolkit.
Sponsor RWE Connect 2026
Meet the Evidence and Methods Buyers in Boston
The teams that build comparators and defend the methods gather at RWE Connect 2026: 150+ attendees, around 60% at Director or VP level and above.
RWE Connect 2026
Get the RWE Study Methods Primer
A plain-English guide to the core real-world evidence methods, including synthetic control arms. See the methods, then meet the people applying them in Boston.
- How synthetic controls are constructed
- The matching methods that make them credible
- Where the methods are heading in 2026
Free. Instant download. No obligation.
Synthetic Control Arms: Common Questions
What is a synthetic control arm?
A synthetic control arm is a comparator built from patient-level real-world data that is statistically matched or weighted to resemble the treated group, so a single-arm trial can be interpreted as if it had a randomized control.
What is the difference between a synthetic and an external control arm?
A synthetic control arm is a specific type of external control. An external control is any comparator drawn from outside the trial, while a synthetic control is built at the patient level using matching or weighting to balance covariates with the treated group.
What is the difference between a synthetic and a historical control?
A historical control uses a whole prior cohort, often unadjusted. A synthetic control matches or weights patients at the individual level to balance measured characteristics with the treated group.
How is a synthetic control arm built?
By defining the target trial, assembling patient-level real-world data, selecting matching variables, applying matching or weighting such as propensity scores or MAIC, checking covariate balance, and comparing outcomes.
What is MAIC?
Matching-adjusted indirect comparison (MAIC) reweights patient-level data from one study so its characteristics match an aggregate comparator, a common technique for building synthetic comparators.
What matching methods are used?
Propensity score matching, inverse probability weighting, MAIC, exact and nearest-neighbor matching, standardization, and covariate-balancing approaches.
Are synthetic control arms accepted by regulators?
In appropriate settings, yes, within FDA and EMA frameworks, when the data and matching methods are fit for the question. They are most established in oncology and rare disease.
What data is used to build a synthetic control arm?
Patient-level real-world data such as electronic health records, registries, natural history studies and patient-level data from prior trials, with enough overlap to match the treated group.
How do you validate a synthetic control arm?
By pre-specifying the estimand, checking covariate balance and overlap, running sensitivity analyses for unmeasured confounding, and reporting the methods transparently.
When should a synthetic control arm be used?
When a randomized control is not feasible or ethical, such as in rare diseases or single-arm trials, and rich patient-level data exists to build a balanced comparator.
What is RWE Connect 2026?
RWE Connect 2026 is a two-day real-world evidence summit in Boston bringing together the RWE, HEOR and methods leaders who generate and apply real-world evidence, with 40+ speakers and 150+ attendees.
When and where is RWE Connect 2026?
14 to 15 October 2026 at the Hampton Inn by Hilton, Boston Seaport District, Boston, MA.
