Research methods
Randomised withdrawal designs
Plain-English explainer on randomised withdrawal designs such as SURMOUNT-4 and what they can and cannot prove.
After an open-label lead-in establishes tolerability and response, randomised withdrawal designs randomise to continue vs withdraw to placebo.
Why they are useful
They directly characterise the contribution of ongoing therapy versus residual carry-over effect and lifestyle change.
Why they are limited
The trial population is enriched for responders and tolerators from the lead-in. The result generalises to that enriched group, not to the original ITT population.
Key takeaways
- Randomised withdrawal designs answer the "keep going or stop" question in responders.
- They do not generalise to the broader ITT population.
- Formal statistical training.
- Individual treatment, prescribing or dosing advice.
- Permission to skip the original publication of any trial cited.
Sources are tagged by class. Regulatory documents, peer-reviewed publications and trial registry records are preferred. Manufacturer disclosures and conference material are accepted where peer-reviewed publication is not yet available; preprints are flagged.